Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition)

Abstract With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de‐intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full‐cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence‐based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes.

international practice, people 65 years or older are defined as older adults, and patients 65 years or older with diabetes are defined as older patients with diabetes, 2 including those diagnosed with diabetes before or after the age of 65 years.With the trends of aging in China and growing demands for diabetes management in older people, an urgent need exists to standardize the management of older patients with diabetes.
China's Medium-to-Long Term Plan for the Prevention and Treatment of Chronic Diseases (2017-2025), issued by the General Office of the State Council, highlights that, by 2025, the number of managed patients with diabetes will reach 40 million, and the standardized management rate of patients with diabetes is expected to reach 70%. 3 The general principles of diabetes diagnosis and treatment may apply to older patients; however, older patients with diabetes require particular considerations regarding blood glucose management methods, goal setting, and principles of drug choice, given the high frequency of multiple complications and/ or comorbidities, atypical symptoms, and poor self-management, and the high risk of hypoglycemia.Therefore, an urgent need exists for standardizing and refining guidance for the management of the diagnosis and treatment of older patients with diabetes, to improve their clinical prognosis.Three authorities, the International Diabetes Federation, the American Diabetes Association, and the Endocrine Society, have published guidelines or consensus statements on diabetes in older people, which provide guidances and serve as references for the clinical diagnosis and treatment of diabetes in older people.In 2021, experts in diabetes, geriatrics, and related fields, organized by the National Center of Gerontology, the Chinese Society of Geriatrics, and the Diabetes Professional Committee of Chinese Aging Well Association, jointly compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). 4In 2022, targeting type 2 diabetes mellitus (T2DM) in older people in China, researchers released the Clinical Guidelines for Prevention and Treatment of Type 2 Diabetes Mellitus in the Elderly in China (2022 Edition). 5Those guidelines have played important roles in promoting the standardized diagnosis and treatment of diabetes in older people in China.
In the past 3 years, extensive research results have emerged in the field of diabetes mellitus in older people; new medications for controlling diabetes mellitus and its complications have been introduced; and evidence from clinical studies has accumulated.
Consequently, the guideline editorial committee updated the The guideline, like the previous version, discusses issues associated with management of diabetes mellitus in older people in the greatest detail possible, focusing on aspects that significantly affect patients' overall health status and quality of life, and differs from the general considerations for adults with diabetes mellitus; these aspects include epidemiology of diabetes and its complications in older people; clinical characteristics of diabetes in older people; comprehensive geriatric assessment (CGA); and management of blood glucose, atherosclerotic cardiovascular disease (ASCVD) risk factors, and acute and chronic complications.The management of risk factors for ASCVD, acute and chronic complications, as well as the management of comorbidities and special conditions in older patients with diabetes are discussed in depth.The guideline also highlights the need for stratified and highly individualized management strategies, given the considerable heterogeneity among older patients with diabetes.In addition, the guideline continues to recommend the simple treatment concept and the de-intensified treatment strategy proposed in the prior version.In this update, the editorial committee searched for and organized evidence regarding diabetes in older people over the past 3 years, paying particular attention to evidence regarding diabetes in older people in China.This version of the guideline provides specific scales for comprehensive health assessment, which are more clinically practical, and recommends anti-hyperglycemic drug treatment pathways for older patients with diabetes with various complications or comorbidities and related risks, thus further advancing the concept of clinical outcomeoriented comprehensive blood glucose management.Furthermore, in the management of ASCVD risk factors, management goals have been adjusted according to the most recent clinical evidence.
The guideline is based on the most recent evidence-based medicine, to guide and help clinicians perform all-around and full-cycle standardized integrated management for older patients with diabetes in China and improve their clinical outcomes.

| G U IDAN CE FOR COMPIL ATI ON S
In recent years, as new diabetes drugs have continued to emerge, the relevant clinical research evidence has been enriched, and the prior guidelines and consensus no longer met current clinical diagnosis and treatment needs.In 2021, by integrating the most recent evidence regarding diabetes in older people in China and other countries, and clinical practice in China, the Expert Committee compiled the first guideline for diabetes mellitus in older people in China.The release of the guideline gained widespread attention, with a read count exceeding 160,000, and was widely praised in the field.A evidence is based on multiple RCTs or meta-analysis.Level B evidence is based on a single RCT or multiple non-RCTs.Level C evidence is based on only the consensus opinion of experts and/or the results of small-scale studies, retrospective studies, or registration studies.The members of the Guideline Writing Group stated each recommendation, presented relevant evidence, and described the level of evidence to the Expert Panel members, who then confirmed the literature and evidence.All Expert Group members participating in the discussion and formulation of final opinions signed a statement on conflicts of interest.The full text was compiled in accordance with the fundamental specifications for the formulation of clinical guidelines.

| CHAP TER 1: EPIDEMI OLOGY OF D IAB E TE S AND ITS COMPLI C ATI ON S IN OLDER PEOPLE
The prevalence of diabetes increases with age, thus exhibiting an age-associated effect. 6According to data from the International Diabetes Federation in 2019, China has approximately 35.5 million patients with diabetes ≥65 years old, ranking first worldwide; these patients account for one-quarter of all older patients with diabetes worldwide and are on the rise. 7A large cross-sectional study on the mainland Chinese population published in 2020 has shown that the prevalence of diabetes is 28.8% and the prevalence of prediabetes is 47.8% between 60 and 69 years old, while the prevalence of diabetes is 31.8% and the prevalence of prediabetes is 47.6% in people over 70 years old, according to the 2018 diabetes diagnostic criteria of the American Diabetes Association.Compared with other age groups, the prevalences of diabetes and prediabetes in the age group over 60 years old are the highest, the prevalences of diabetes in elder women is higher than that in the men. 8 precise, high-quality data on the incidence of diabetes complications in older people are currently available.Diabetes is associated with risks of death due to ischemic heart disease, stroke, chronic liver disease, neoplasm, female chronic urinary and reproductive system diseases, etc. 9 ; moreover, the mortality among older people is significantly higher in those with diabetes rather than those without diabetes. 10der people are prone to a variety of concurrent chronic diseases, and the proportion of older people with T2DM with hypertension and/or dyslipidemia is as high as 79%. 11When formulating the clinical diagnosis and treatment plan, clinicians should conduct comprehensive assessments to control the damage caused by multiple metabolic disorders in a safe and beneficial manner, delay diabetes progression, and substantially improve patient's quality of life.

| Diagnosis of diabetes in older people
The 1999 WHO diagnostic criteria for diabetes are used, that is, the fasting plasma glucose (FPG), random plasma glucose, or 2-h plasma glucose (2hPG) during an oral glucose tolerance test (OGTT) are primarily used for the diagnosis of diabetes, however, the diagnosis must be confirmed by a repeated test when a patient has no typical clinical symptoms of diabetes.
For patients without typical diabetes symptoms, the test should be reperformed on another day to provide confirmation (Table 1).The WHO recommends using glycosylated hemoglobin A1c (HbA 1c ) ≥6.5% as the cut point for diagnosing diabetes. 12HbA 1c tested by laboratories in China using standardized methods and strict quality control can also be used as a diagnostic indicator for diabetes.However, in conditions such as sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, hemodialysis, recent bleeding or transfusion, and erythropoietin therapy, the diagnosis of diabetes must be based on the measurement of venous plasma glucose levels, and HbA 1c cannot be used. 13Age is associated with HbA 1c levels in the Chinese population. 14,15

| Classification and characteristics of diabetes in older people
Diabetes in older people refers to diabetes in individuals ≥65 years old, including those diagnosed before or after 65 years old.Older patients with diabetes are mainly T2DM, but also include T1DM, and other types of diabetes.New-onset T1DM is rare in the older population.
Most T1DM is attributed to latent autoimmune diabetes in adults or may be T1DM previously diagnosed before the age of 65 years.In the guideline, diabetes in older people is classified into T1DM, T2DM, or specific types of diabetes (e.g., monogenic diabetes, exocrine pancreatic diseases, or drug-or chemical-induced diabetes) according to the WHO 1999 etiological classification system of diabetes.The older population is a high-risk group for malignancies, and, given the use of immune checkpoint inhibitors, immune checkpoint inhibitor-associated diabetes has been reported. 16Such diabetes is currently recommended to be classified as drug-induced diabetes within the category of specific types of diabetes.
In recent years, researchers have proposed several new diabetes classification schemes, each of which has limitations.The classification of older patients with diabetes is important, but greater attention should be paid to the uniqueness of these patients.Most older patients with diabetes do not have typical clinical symptoms (i.e., polydipsia, polyuria, polyphagia, and unexplained weight loss); older patients with diabetes are prone to multiple complications and/or concurrent diseases, which may manifest first.Because diabetes is associated with a variety of malignancies-e.g., 68% of patients with pancreatic cancers have elevated blood glucose (impaired glucose tolerance or diabetes) 17,18 -tumor screening is recommended for newly diagnosed older patients with diabetes.

| Primary prevention
For older adults with risk factors for diabetes, the goal is to reduce the incidence of diabetes.Aging is one of the risk factors of diabetes, and the older population is susceptible to diabetes.
Health education should be carried out among the older population, especially in people with prediabetes, to reduce the risk of diabetes through passing on health knowledge and improvement of lifestyle (e.g., appropriate diet and exercise, etc.).In addition, it is necessary to carry out blood glucose and HbA 1c screening and strengthen the ASCVD risk factors management of the older population (e.g., cessation of smoking, alcohol limitation, control of blood pressure and blood lipids, etc.) and monitor blood glucose regularly in older patients taking statin. 19

| Secondary prevention
For older adults who already have diabetes, the goal is to reduce the incidence of diabetes complications.Older patients with diabetes should be diagnosed as early as possible.Comprehensive complications screening and important organ function assessments should be performed at the time of diagnosis, lifestyle intervention should be guided and reasonable treatment should be carried out based on patient's condition, to reduce the incidence of complications.

| Tertiary prevention
For older patients with complications of diabetes, the goal is to reduce patients' disability and mortality rates and improve their quality of life.For these patients, timely and effective integrated treatments and multidisciplinary management should be adopted to prevent or delay the progression of diabetes complications, lower the disability and mortality rates of older patients, and improve their quality of life.

| CHAP TER 4: COMPREHEN S IVE G ERIATRI C A SS E SS MENT OF OLDER PATIENTS WITH D IAB E TE S
CGA is a multidisciplinary process conducted to determine the physical, functional, mental, and social problems in older people, so that a coordinated plan of care can be developed to maintain

Key points
1. CGA is performed for older patients with diabetes through a multidisciplinary team approach.(A) 2. According to the assessment results, older patients with diabetes are divided according to health status into a good health status (Group 1), intermediate health status (Group 2), and poor health status (Group 3).(A) or HbA 1c ≥6.5% For patients without typical diabetic symptoms, another test is required for confirmation.
Note: Random plasma glucose refers to blood glucose at any time of the day, regardless of the time of the last meal, and cannot be used to diagnose impaired fasting glucose or impaired glucose tolerance; fasting state refers to no intake of calories for at least 8 h; HbA 1c should be tested in laboratories meeting the standardized measurement requirements.
and improve their health and functional status, and maximize their quality of life.Currently, the CGA scales commonly used in China include the Comprehensive Geriatric Assessment Scale for Chinese Elderly, 20 the Standard for Chinese Healthy Elderly Assessment Scale, 21 and the Multidimensional Health Assessment Scale of the Elderly. 22e health status of older patients with diabetes varies greatly among individuals, and often accompanied by varying degrees of cognitive disorders and complex underlying diseases.Therefore, CGA should be performed through a multidisciplinary team approach, in collaboration with clinicians, dietitians, rehabilitation therapists, and nurses, to develop an individualized regimen to which each patient can adhere over the long term.
According to the above-mentioned scales, the health status of older patients with diabetes, including the comorbidity pro-    Based on the overall health assessment of older patients with diabetes, depending on whether they use drugs that increase the risk of hypoglycemia, the recommended glycemic goals are shown in Table 3.For older patients taking drugs that increase the risk of hypoglycemia, the HbA 1c goal should not be too low.Therefore, a lower limit of the glycemic goal should be clearly set for these patients, to mitigate the risk of hypoglycemia.Glucose indicators such as the time in range (TIR), time below range (TBR), time above range (TAR), and coefficient of variation (CV) can reveal glucose variability.According to international consensus, these indicators can be used as supplementary glycemic goals 28 (Table 4).

| CHAPTER 7: LIFEST YLE INTERVENTION OF OLDER PATIENTS WITH DIABETES
Lifestyle intervention is the fundamental treatment of older patients with diabetes, all of whom should receive lifestyle therapy.For some older patients with diabetes in good health (Group 1) with mildly increased blood glucose levels, their targeted glucose can be achieved by only lifestyle intervention.

| Medical nutrition therapy
Medical nutrition therapy (MNT) is fundamental and should be applied through the whole course of diabetes mellitus management.

TA B L E 4
Glucose variability control goals for older patients with diabetes.It is difficult for the elderly to change their diet habits.It is possible to make appropriate adjustments to develop individualized nutritional therapy plans based on their dietary habits, considering factors such as the degree of willingness to modify dietary structure and the ability to obtain healthy food, and considering metabolic control goals, total calorie intake, and nutritional quality.MNT should be coordinated with the patient's overall lifestyle, including their exercise status and medication use.

Key points
Because muscle mass in older patients are tend to be low and a sufficient energy intake can avoid muscle proteolysis, the protein intake, predominantly the intake of high-quality protein rich in branched-chain amino acids such as leucine, should be increased as appropriate. 30Healthy older people need to ingest 1.0-1.3g kg −1 d −1 of protein, those with concurrent acute/chronic diseases need to ingest 1.2-1.5 g kg −1 d −1 of protein, and those with concurrent sarcopenia or severe malnutrition need to ingest at least 1.5 g kg −1 d −1 of protein. 31In addition to animal protein, plants with high-quality protein are also acceptable. 32Carbohydrates are the main energy source of older patients with diabetes in China, and monitoring carbohydrate intake is an important strategy for achieving blood glucose goals, but there is still no consensus on the optimal amount of carbohydrate intake for older patients with diabetes.Intake of foods rich in dietary fiber while consuming carbohydrates can delay blood glucose elevation, reduce glycemic variability, and improve lipid control.As dietary fiber increases the feeling of fullness and delays gastric emptying, older patients with gastroparesis and functional gastrointestinal disorders should avoid excessive intake.Attention should be paid to patients' ingestion sequence of carbohydrate, protein, and vegetables, since later ingestion of carbohydrates can reduce the speed of increase in patient's postprandial plasma glucose level. 33For older diabetes mellitus patients with long-term imbalanced diet, attention should also be paid to supplementation of vitamins and minerals.Compared to the non-diabetic population, older patients with diabetes are at higher risk of malnutrition and more likely to develop sarcopenia and frailty. 34As a result, these patients should avoid excessive limitation of energy intake, pay attention to rational diet and balanced nutrition, and be alert to malnutrition.

| Exercise therapy
Exercise is one of the most effective methods for preventing and managing older people with diabetes, 35,36 and lifestyle intervention based on regular exercise can improve the insulin sensitivity of patients with diabetes. 37However, older patients with diabetes often suffer from multiple concurrent chronic diseases, for example, osteoarthropathy, which causes a decline in their walking ability, and cerebrovascular disease, peripheral neuropathy, or severe sarcopenia, which make patients are prone to fall.Therefore, it is necessary to carry out exercise risk evaluation for older patients with diabetes before exercise therapy, which is based on patients' medical history, family history, physical activity ability, and related medical examination results.and the metformin dosage should be adjusted accordingly. 45r older patients with an eGFR of 45-59 mL min −1 (1.73 m 2 ) −1 , dosage decreases should be considered, and when the eGFR is <45 mL min −1 (1.73 m 2 ) −1 , discontinuation should be considered. 45Metformin is contraindicated in older patients with severe infections, trauma, and conditions causing tissue hypoxia (such as decompensated heart failure or respiratory failure).
For patients with eGFR ≥60 mL min

| Sulfonylureas
The commonly used sulfonylureas include glibenclamide, gliclazide, glipizide, gliquidone, and glimepiride.Although sulfonylureas have a noticeable hypoglycemic effect, they carry risks of hypoglycemia and weight gain.Long-acting sulfonylureas tend to exhibit the above adverse effects more frequently, particularly in older people, thus necessitating cautious use. 47Short-acting formulations, sustained-release formulations, and controlled-release preparations with consistent and stable concentrations are preferred after careful evaluation of their benefits and risks.Sulfonylureas are a Grade 3 glycemic recommendation for older patients with T2DM.
When co-administered with drugs that are cleared by hepatic P450 enzymes such as CYP2C9 and CYP2C19 (e.g., statins, antibiotics, selected cardiovascular agents, and proton pump inhibitors), vigilance is imperative to avoid hypoglycemic events 48 and other adverse events.Gliquidone, with a plasma half-life of 1.5 h and only 5% of its metabolites cleared via the kidneys, is a preferred sulfonylurea choice for older patients with T2DM with mild to moderate renal impairment.

| Glinides
The main glinides are repaglinide and nateglinide.The hypoglycemic effect and the risk of weight gain of glinides are similar to that of sulfonylureas, while the risk of hypoglycemia is lower. 49

| Thiazolidinediones
Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are insulin sensitizers that exert glycemic effects by enhancing the sensitivity of insulin in skeletal muscle, liver, and adipose tissues.
When used independently, these drugs generally do not induce hypoglycemia, but when they are combined with insulin or insulin secretagogues, the risk of hypoglycemia is elevated. 49TZDs are classified as a Grade 3 glycemic recommendation for older patients with T2DM.Studies have indicated that pioglitazone can reduce the composite endpoint risk of all-cause mortality rate, non-fatal myocardial infarction, and stroke in T2DM patients with high risk of macrovascular complications. 51A meta-analysis has revealed that pioglitazone may decrease the risk of recurrent stroke in patients who have experienced prior ischemic stroke or transient ischemic attack with insulin resistance, prediabetes, or diabetes. 52trospective cohort studies have suggested that pioglitazone decreases the risk of major cardiovascular events and dementia in older patients with T2DM. 53Thus, TZDs can be a choice for older patients with T2DM with severe insulin resistance.However, TZDs may increase the risk of weight gain, edema, fractures, and heart failure. 54Caution is recommended when these drugs are used in older patients with T2DM who are receiving insulin or who have congestive HF, osteoporosis, or risks of falls or fractures.

| Dipeptidyl peptidase IV inhibitors
Dipeptidyl peptidase IV inhibitors (DPP-4 inhibitors), such as sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin, trelagliptin, retagliptin, and teneligliptin, are among the Grade 1 glycemic treatments recommended for older patients with T2DM in recent Chinese and international guidelines and/or consensus statements.These drugs inhibit the activity of the DPP-4 enzyme, thus increasing endogenous glucagon-like peptide-1 (GLP-1) levels.GLP-1 facilitates glucose concentration-dependent endogenous insulin secretion while suppressing glucagon secretion, thereby lowering blood glucose levels. 57Currently most approved DPP-4 inhibitors on the Chinese market are administered daily (or twice daily for vildagliptin), except for trelagliptin, which is administered weekly.When used alone, these drugs generally do not induce hypoglycemia.DPP-4 inhibitors have neutral effects on body weight and cause few gastrointestinal reactions 58 and therefore are suitable treatment choice for older patients. 59In older patients already receiving stable basal insulin therapy, addition of linagliptin has been demonstrated to enhance glycemic control and help older patients achieve their goals safely. 60PP-4 inhibitors are categorized as Grade 1 recommended glycemic drugs for older patients with T2DM.
2][63] Linagliptin specifically does not elevate the risk of renal composite outcomes, defined as death from kidney disease, progression to terminal kidney disease, or a sustained eGFR decline ≥40%, in older patients. 62However, saxagliptin has been associated with an elevated risk of heart failure hospitalization. 63 dose adjustment is warranted when linagliptin is administered in patients with hepatic insufficiency or saxagliptin is administered in patients with liver impairment; sitagliptin does not require dosage adjustment in patients with mild to moderate hepatic insufficiency.However, caution should be exercised with alogliptin in patients with liver disease, and vildagliptin is contraindicated for patients with abnormal liver function (serum alanine aminotransferase or aspartate transaminase levels exceeding three times the upper limit of normal or increasing continuously).Linagliptin and teneligliptin can be used in older patients with any level of kidney function without dosage adjustment.For the other DPP-4 inhibitors, dosage adjustment or discontinuation may be necessary, according to kidney function.If pancreatitis is suspected in a patient, the use of DPP-4 inhibitors should be terminated.
These drugs are effective and safe in older patients. 658][69][70] SGLT2 inhibitors also play roles in weight loss, particularly in decreasing visceral fat. 71e EMPA-ELDERLY study has demonstrated that empagliflozin decreases body weight without compromising muscle mass and body strength in older patients. 72LT2 inhibitors have demonstrated cardiovascular and renal benefits.A meta-analysis has indicated that SGLT2 inhibitors consistently decrease the risk of 3P-MACE, heart failure hospitalization, and renal outcomes in older patients and other age groups.in both the older subgroup and the general population. 74,75CVOTs also have suggested that dapagliflozin and empagliflozin consistently decrease the risk of hospitalization for heart failure in patients with T2DM, in both the older subgroup and the general population. 74,76nal outcome trials (ROTs) have shown indicated that canagliflozin is associated with diminished risk of cardiovascular death or heart failure hospitalization 77 in both the older patient subgroup and the general population.CVOTs have indicated that dapagliflozin and empagliflozin improve renal outcomes, 78,79 achieving improvements in composite cardio-renal outcomes with dapagliflozin and renal outcomes with empagliflozin in both the older subgroup and the general population.5][76] The EMPA-KIDNEY study has concluded that empagliflozin decreases the risk of renal disease progression or cardiovascular death in patients with CKD (with or without T2DM). 80Moreover, the DAPA-CKD study has suggested that dapagliflozin decreases the risk of worsening renal function, terminal-stage renal disease, and death from renal or cardiovascular diseases in patients with CKD (with or without T2DM) and has indicated similar effects in the older subgroup and the general population. 81,827][88] The CVOT study has concluded that ertugliflozin decreases the risk of heart failure hospitalization without increasing the risk of 3P-MACE and cardiovascular death and has indicated consistent results in the older subgroup and the general population. 89For henagliflozin, studies on its efficacy regarding cardiac function or urinary albumin in patients with T2DM are ongoing.
Common adverse reactions of SGLT2 inhibitors include genitourinary system infection and hypovolemia.Reports of ketoacidosis have also been observed in post-marketing clinical surveillance, and the risk may be elevated in older patients. 90In addition, SGLT2 inhibitors lower blood pressure and promote weight loss.Therefore, special attention should be paid to monitoring patient blood pressure and avoiding hypotension.Caution should be exercised when these drugs are administered to frail patients.If the eGFR is empagliflozin should not be initiated.However, if empagliflozin or dapagliflozin has already been used, the treatment should ideally not be discontinued, unless patients are intolerant or require renal replacement therapy. 91These drugs decrease glucose levels by increasing urinary glucose excretion; therefore, for lowering blood glucose, dapagliflozin is not recommended when the eGFR is <45 mL min −1 (1.73 m 2 ) −1 , and empagliflozin is not recommended when the eGFR is <30 mL min −1 (1.73 m 2 ) −1 .

| Glucagon-like peptide-1 receptor agonists
GLP-1RAs bind the GLP-1 receptor, thereby promoting insulin secretion and inhibiting glucagon secretion, and decreasing blood glucose, in a glucose concentration-dependent manner.These drugs slow gastric emptying, inhibit the appetite center, and decrease eating.3][94] The risk of hypoglycemia is low when GLP-1RAs are used alone.6][97] The GLP-1RAs currently approved in China include exenatide, liraglutide, lixisenatide, dulaglutide, beinaglutide, loxenatide, and semaglutide, all of which are subcutaneous injection preparations.Liraglutide is administered once per day at any time.Lixisenatide is administered once per day before any meal.
Exenatide weekly formulation, loxenatide, dulaglutide, and semaglutide are administered once per week at any time.The flexible administration of GLP-1RAs supports compliance among older patients with diabetes, and weekly formulations are further increasing compliance.
Some GLP-1RAs have proven cardiovascular benefits.A metaanalysis has indicated that these drugs significantly decrease the risk of 3P-MACE, cardiovascular death, and stroke, and their effects are consistent in both older people and non-older population. 73GLP-1RAs also decrease the risk of adverse renal outcomes, primarily through decreasing urinary albumin excretion. 98 cular disease or at high risk. 99Dulaglutide has shown evidence of primary prevention in T2DM patients with high risk of ASCVD; and the results from baseline heterogeneity analysis are consistent in patients aged ≥66 years and <66 years. 99Liraglutide significantly reduces the risk of 3P-MACE in T2DM patients complicated with high risk of cardiovascular diseases. 100Semaglutide significantly decreases the risk of 3P-MACE in patients with T2DM with cardiovascular disease, chronic HF, CKD, age >60 years, or high cardiovascular risk factors.In the baseline heterogeneity analysis, the results were consistent for patients ≥65 years and <65 years of age. 101CVOTs of lixisenatide and exenatide have demonstrated no increased risk of MACE. 102,103[101][102][103] Studies have explored the clinical benefits of combining SGLT2 inhibitors and GLP-1RAs.A meta-analysis has suggested that, compared with single drug treatment, the combination of two classes of drugs confers more benefits regarding blood glucose, blood pressure, and blood lipid. 104A retrospective cohort study has found that, compared with single drug treatment, combined therapy with SGLT2 inhibitors and GLP-1RAs achieves better all-cause mortality and cardiovascular benefits. 105However, little high-quality evidence to date has demonstrated the clinical benefits of combined therapy with these two drugs in the older population.
GLP-1RAs that are easy to use and provide extra benefits other than glucose lowering are recommended. 106The main adverse reactions of GLP-1RAs are nausea, vomiting, diarrhea, decreased appetite, other gastrointestinal adverse events, and slowed gastric emptying.Vigilance is necessary to avoid inducing or aggravating malnutrition, sarcopenia, or frailty in older patients with T2DM.In addition, some studies have observed an increased risk of adverse reactions such as intestinal obstruction, gastroparesis, and pancreatitis after use of GLP-1RAs. 107Therefore, for older patients, it is necessary to assess their potential risks and benefits.

| Insulin
If lifestyle interventions and non-insulin treatments fail to achieve glycemic goals in older patients with T2DM, insulin therapy may be introduced.Before initiation of insulin therapy in older patients, factors such as the overall health, characteristics of elevated blood glucose, and risk of hypoglycemia must be adequately considered.
The benefit-to-risk ratio should be assessed for each individual to formulate customized therapies.
For the initial insulin treatment, the preferred choices are basal insulin, biphasic insulin, or a fixed combination of basal insulin and GLP-1RAs, because their ease of administration and high compliance make them suitable for most older patients. 47The preferred choice of basal insulin should be a dosage form that maintains a stable concentration in the blood (e.g., Insulin Glargine U100, Insulin Degludec, and Insulin Glargine U300).Basal insulin should be administered in the morning to decrease the risk of hypoglycemia, particularly nocturnal hypoglycemia.The starting dose may be calculated according to the body weight and is usually set at 108 For patients with HbA 1c >8.0%, a dose of 0.2-0.3U kg −1 d −1 may be used as the starting basal dose. 109The dosage is adjusted every 3 to 5 days depending on the fasting blood glucose level until the goal is reached.If the fasting blood glucose goal is reached, but the goal for HbA 1c has not been reached, focus should be placed on postprandial blood glucose, and prandial insulin may be introduced if necessary. 2Basal insulin combined with prandial insulin (three times per day) mimics the human body's physiological insulin secretion pattern, but the complicated administration regimen may compromise patients' compliance with long-term therapy.In addition, this regimen is not suitable for older patients with poor health status (Group 3) or with short life expectancy.Biphasic insulin injection once or twice per day is as effective as multiple injections but requires fewer administration doses, thus supporting patient compliance. 1102][113] Premixed insulin requires less frequent administration than a basal-prandial combination.However, in older patients, particularly those with long disease duration, poor pancreatic islet function, or irregular meals, premixed human insulin or premixed insulin analogues may increase the risk of hypoglycemia. 114 older patients with diabetes have HbA 1c >10.0% or symptoms of hyperglycemia (e.g., polydipsia or polyuria), or show evidence of catabolism (e.g., weight loss) or severe hyperglycemia (fasting blood glucose >16.7 mmol L −1 ), short-term insulin therapy may be applicable, depending on patients health status and treatment goals.Except for patients with pancreatic islet failure, older patients with diabetes should promptly decrease the frequency of insulin injections, and their antidiabetic therapy should be optimized after short-term insulin therapy has stabilized the blood glucose and addressed the high glucose toxicity. 115 older patients with diabetes, the strategy for insulin therapy should involve de-intensification.For patients already receiving insulin, assessments should be conducted to determine whether insulin therapy is necessary and whether the regimen can be de-intensified.Multiple injections of insulin are not recommended for older patients with diabetes who are senile or have short life expectancy or poor health status (Group insulin combined with a DPP-4 inhibitors is also advisable; 60,113,116,117 Attempt to switch from premixed insulin to basal insulin to simplify the regimen and decrease the risk of hypoglycemia.

| Fixed combination therapy
As T2DM progresses, combination therapy is often required.Several studies have examined fixed combination therapies in the older population.The GIFT study has indicated that switching from a co-administered dual therapy with metformin and DPP-4 inhibitors to an FDC regimen of the two improves glycemic control and achieves more significant blood glucose improvement in older patients, probably because of increased compliance. 119The LixiLan series studies and the DUAL series studies have verified the efficacy and safety of Insulin Glargine-Lixisenatide FRC and Insulin Degludec-Liraglutide FRC, respectively, in patients with T2DM.1][122][123][124][125] Post hoc analysis of the LixiLan-L/O study and multiple DUAL series studies have indicated that, compared with therapies with a single component, Insulin Glargine-Lixisenatide FRC and Insulin Degludec-Liraglutide FRC are effective, safe, and tolerable in older patients. 116,117,126

| Recent advancements in glycemic drugs
In recent years, two newly approved classes of glycemic drugs with novel mechanisms of action have been introduced in China for the treatment of T2DM: peroxisome proliferator-activated receptor (PPAR) pan-agonists and glucokinase activators.One representative PPAR pan-agonist is chiglitazar sodium, a next-generation non-TZD insulin sensitizer.This drug simultaneously activates the PPARα, γ, and δ subtype receptors, thereby enhancing insulin sensitivity and consequently lowering blood glucose levels. 127A representative glucokinase activator is dorzagliatin, which regulates glucokinase activity in a glucose-dependent manner, thus improving blood glucose regulation stability and exhibiting glycemic effects. 128Currently, clinical application of these two classes of drugs specifically in older patients with T2DM remains limited; therefore, more data is needed to demonstrate their effectiveness and safety in older patients with T2DM.

| Treatment pathways
Therapeutic drug choices should be based on the health sta-

Not achieve HbA1c target
after single-drug therapy for more than 3 months, combination therapy with drugs with different mechanisms should be considered.However, caution is advised to avoid combining drugs that may increase the risk of hypoglycemia and other adverse events.For older patients who do not reach glycemic goals with standardized non-insulin treatments, insulin therapy should be initiated promptly.The insulin treatment plan should include comprehensive patient education on preventing and managing hypoglycemia and proper insulin injection techniques to minimize the occurrence of hypoglycemia and other adverse events associated with insulin injection.
For patients with poor health status (Group 3), including those in an end-of-life stage, following the above pathways for treatment selection is not recommended.Instead, the approach should be F I G U R E 3 Pathway of insulin therapies for older T2DM patients.GLP-1RA, glucagon-like peptide-1 receptor agonist; T2DM, Type 2 diabetes mellitus.Insulin therapy can be combined with noninsulin therapies.However, it is not advised to combine insulin with sulfonylureas or glinides.In terms of insulin, both human insulin and insulin analogues are included, and insulin analogues should be preferred.Only premixed insulin analogues can be administrated three times a day, but premixed human insulin or biphasic insulin cannot.The treatment pathway is intended for elderly patients with good (Group 1) and intermediate (  4 Pathway of short-term insulin therapies for older T2DM patients.HbA 1c , glycated hemoglobin; T2DM, Type 2 diabetes mellitus.In terms of insulin, both human insulin and insulin analogues are included, and insulin analogues should be preferred.Premixed insulin analogues can be administered three times a day, whereas premixed human insulin cannot.Non-insulin therapy may be discontinued during the short-term insulin therapy.Once the hyperglycemic state is relieved, the treatment strategy should be reevaluated and optimized. HbA 1c >10.0%，or with symptoms of hyperglycemia (e.g.polydipsia or polyuria) , or catabolism (e.g.weight loss) or severe hyperglycemia (fasting blood glucose>16.7 mmol/L)

Grade 3 recommendation
based on aspects including these patients' vital organ function, drug treatment response, and hypoglycemia risk, to establish relatively loose glycemic goals.The fundamental principles include avoiding both hypoglycemia and severe hyperglycemia.Respecting the wishes of patients and their families, and selecting an appropriate glycemic therapy accordingly is essential.The use of oral drugs and/ or long-acting/ultra-long-acting basal insulins with a lower risk of hypoglycemia, such as Insulin Glargine U100, Insulin Degludec, and Insulin Glargine U300, is considered safer than multiple daily injections of rapid-acting insulin or premixed insulin.This approach also facilitates easy dosage adjustment.The use of drugs with high risk of hypoglycemia and substantial weight loss is not recommended.

| CHAP TER 9: A SC VD AND RIS K FAC TOR MANAG EMENT IN OLDER PATIENTS WITH D IAB E TE S
ASCVD includes coronary artery disease, cerebrovascular disease, and peripheral vascular disease caused by atherosclerosis and is a major cause of disability and death among people with T2DM. 129e risk of cardiovascular disease in patients with T2DM is more than twice that in people without diabetes. 130In clinical practice, actively screening and treating risk factors for cardiovascular disease is important.For older patients with diabetes mellitus who

| Screening and evaluation
Multiple macrovascular complications may progress for years before the diagnosis of diabetes, thus making the management of ASCVD challenging.Consequently, active screening for ASCVD and related risk factors is critical.Patients are recommended to undergo blood pressure monitoring at each visit, and to undergo systemic evaluation of ASCVD risk factors (including overweight and obesity, hypertension, dyslipidemia, smoking, and family history of early onset coronary heart disease, CKD, and proteinuria) at least annually; for older patients with diabetes with the above ASCVD risk factors, ultrasonic evaluation of the carotid arteries and lower extremity arteries should be actively performed to assess any peripheral vascular disease, so that the risk factors can be identified and intervention can occur as early as possible.

| Cardiovascular risk factor management
1. Hypertension: Older patients with diabetes have elevated risk of hypertension, which is an independent risk factor for cardiovascular disease.After other risk factors are controlled, every 10 mmHg (1 mmHg = 0.133 kPa) increase in SBP is associated with a 30% higher risk of ischemic heart disease and ischemic stroke, 131 whereas anti-hypertensive therapy can decrease the occurrence and death risks of cardiovascular events in patients with diabetes. 132In older patients, the benefits of Adding statin therapy is recommended for older patients with diabetes mellitus.However, high-quality evidence regarding the optimal lipid control targets for older patients with diabetes mellitus remains lacking.
Additionally, attention should be paid to the potential adverse reactions that may occur with statin therapy.(B) 5.For older patients with diabetes, routine use of aspirin is not recommended for primary prevention, but low dose anti-hypertensive therapy have also been extensively demonstrated in clinical studies. 133Control goal: Currently, research specifically examining blood pressure control targets for older patients with diabetes mellitus is lacking.The blood pressure target for older patients with diabetes mellitus should be individualized, considering the benefit-to-risk ratio.In the ACCORD BP study, an intensive blood pressure control (SBP target <120 mmHg), compared with standard blood pressure control (SBP target <140 mmHg), did not decrease the primary composite endpoint (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), but increased the risk of adverse events such as hypotension and hyperkalemia.134 Results from the STEP study conducted in China and published in 2021 have indicated that, compared with standard blood pressure control (SBP target 130-150 mmHg), intensive blood pressure control (SBP target 110-130 mmHg) decreases the risk of MACE by 26% in older patients without increasing the risk of adverse events such as dizziness or fractures, except for an increased risk of hypotension.In that study, 18.9% and 19.4% of patients in the intensive and standard blood pressure control groups, respectively, were older patients with diabetes mellitus (60-80 years of age).135 The SBP target for older patients with diabetes mellitus is recommended to be set below 130 mmHg to decrease the risk of cardiovascular disease.136 However, blood pressure should be closely monitored to prevent conditions such as orthostatic hypotension, postprandial hypotension, and excessively low diastolic blood pressure.A SBP < 120 mmHg is not recommended as a control goal of older patients with diabetes.137 For patients who are 80 years or older or have a short life expectancy or poor health status (Group 3), the SBP control goal can be appropriately extended to below 150 mmHg. 2 2. Drug choice: ACEIs significantly decrease major cardiovascular adverse events, cardiovascular deaths, and all-cause mortality among patients with diabetes 138 ; and in older patients with diabetes, ACEIs also decrease cardiovascular deaths.139 ARBs have similar effects in patients with diabetes 140 ; and in older people, ARBs significantly decrease stroke.141 ACEIs or ARBs are recommended as the first-line medications for controlling blood pressure in older patients with diabetes 2 but should not be co-administered 140 ; otherwise, hyperpotassemia and acute kidney injury may occur.141 Blood potassium and creatinine levels should be closely monitored during administration.If the blood pressure is inadequately controlled by ACEIs or ARBs alone, calcium channel blockers (CCBs), thiazide diuretics, or β-blockers may be added for lowering blood pressure.2 2. Dyslipidemia: Older patients with diabetes often have dyslipidemia, thus leading to an increased risk of ASCVD.Limited medical evidence supporting lipid lowering therapy in older patients with diabetes is available.On the basis of existing evidence, controlling the LDL-C of older patients with diabetes below 2.6 mmol L −1 , 142,143 and controlling that of older patients with diabetes and concurrent ASCVD below 1.8 mmol L −1 , 142,143 are recommended; however, for patients of 80 years or older, or those with a short life expectancy or poor health status (Group 3), the LDL-C goals should be appropriately relaxed.
Statins can decrease the risk of cardiovascular events 144,145 and all-cause mortality in older patients. 145,146Both the Heart Protection Study DM Subgroup (HPS-DIM) and Collaborative Atorvastatin Diabetes Study (CARDS) have suggested that statins decrease the risk of cardiovascular events in older patients with diabetes. 147,148However, evidence in older patients (80 years or older) with diabetes remains lacking.Studies have shown that ezetimibe plus simvastatin decreases ischemic stroke risk in patients with acute coronary syndrome by 24%, 149 and this benefit is enhanced in patients with concurrent diabetes or other risk factors. 150Older patients with diabetes are recommended to use statins to decrease cardiovascular events and all-cause mortality.If the LDL-C goal can not be achieved with statins alone, ezetimibe or PCSK9 inhibitors may be added with caution. 2,142,143For older patients with diabetes whose triglycerides exceed 5.65 mmol L −1 , fenofibrate may be used to decrease pancreatitis risk, but caution is necessary regarding the increased risk of adverse events when fenofibrate is concomitantly used with statins.Given that older patients with diabetes often have multiple concurrent diseases requiring polymedication, close attention should be paid to monitoring the safety of statins and their interactions with other drugs, and to monitoring changes in liver function and creatine kinase levels.
3. Antiplatelet therapy: The benefits and risks of aspirin antiplatelet therapy should be weighed according to the bleeding risk, risk of underlying cardiovascular disease, compliance with aspirin therapy, and age.Although primary prevention with aspirin decreases cardiovascular events in patients with diabetes, it increases the risk of bleeding events, and older age is associated with higher bleeding risk.According to Aspirin in Reducing Events in the Elderly (ASPREE), in the population of 70 years or older with the risk of cardiovascular disease, aspirin increases the risk of bleeding instead of decreasing the incidence of cardiovascular disease. 151Recent meta-analyses have shown similar results. 152At present, no sufficient evidence indicates that the benefits of aspirin outweigh the risks for primary prevention in older people with diabetes; therefore, routine use of aspirin in these patients for primary prevention of cardiovascular events is not recommended.Older patients with diabetes and concurrent ASCVD are recommended to use low-dose aspirin (75-150 mg day −1 ) for secondary prevention. 2 However, patients of 80 years or older, or those with a short life expectancy or poor health status (Group 3), should be managed individually.Because the most common adverse event of aspirin is gastrointestinal hemorrhage, bleeding risk should be fully evaluated before use.The risk of bleeding is associated with factors including high-dose of aspirin, long-term administration, severe hepatic insufficiency, renal insufficiency, peptic ulcers, hemorrhagic diseases, diminished platelets, use of nonsteroidal anti-inflammatory drugs, and inadequately controlled blood pressure.After aspirin use, patients and their families should be fully educated to identify possible bleeding risks in a timely manner.In addition, concomitant use of proton pump inhibitors (PPIs) may help decrease the risk of gastrointestinal hemorrhage.
4. Cessation of smoking: Smoking increases the risk and mortality of coronary heart disease and stroke, which shows a dose-response relationship 153,154 ; moreover, passive smoking also increases the risk of cardiovascular disease. 155,156In older people, smoking remains an important independent risk factor for cardiovascular disease, and smoking cessation can help decrease the risk of cardiovascular disease.Because people of all ages can benefit from cessation of smoking, older patients with diabetes should be actively encouraged to cease smoking. 157nd increasing the medical burden.Furthermore, the risk of cardiovascular disease is also significantly elevated in people with DKD.

| Screening
At the time of diagnosis, older patients with diabetes should undergo screening and assessment of the urine albumin/creatinine ratio (UACR) and blood creatinine (used to calculate eGFR) to promote identification of early kidney damage.Patients should be followed up at different frequencies according to their renal function status (Table 5). 160,161inical diagnosis should be made according to increased UACR diabetes-induced renal injury accounts for one-third of renal injury in this patient group. 162CR testing with random urine is the simplest screening method, and UACR >30 mg/g is considered elevated; however, strenuous exercise, infection, fever, congestive HF, and significant increases in blood glucose or blood pressure may also cause the UACR to increase.Some patients may develop renal impairment when the UACR remains within the normal range.eGFR is an important tool for evaluating renal function.In general, calculation of eGFR with the CKD Epidemiology Collaboration equation is recommended.163 Older people may have false normal eGFR findings because of low body weight and inadequate protein intake; consequently, the significance of renal function assessment based on the eGFR alone in older people is limited, and the definition of eGFR in older people remains controversial.164

| Treatment
Integrated treatment based on glucose-lowering therapy should be emphasized for older patients with diabetes with concurrent CKD.
1.For patients not receiving dialysis, the recommended daily intake of high-quality protein is 0.8 g kg −1 .Limiting sodium salt intake is recommended because sodium chloride <5 g day −1 or sodium <2 g day −1 can help lower blood pressure and decrease the risk of cardiovascular disease. 165 For glucose-lowering therapy, SGLT2 inhibitors are preferred for older patients with diabetes and CKD.In cases of intolerance or contraindications, GLP-1RAs with evidence of renal protection should be considered, followed by drugs that are essentially not excreted via the kidney, such as linagliptin, repaglinide, and gliquidone.During the use of glucose-lowering medications, attention should be paid to whether dose adjustment is required, according to the eGFR, and the onset of hypoglycemia should be monitored.

For anti-hypertensive therapy, ACEI or ARB can be chosen. If
necessary, these drugs can be co-administered with other types of anti-hypertensive drugs.During the administration, attention should be paid to monitoring blood pressure, renal function, and blood potassium.The achievement of blood pressure control goals is crucial for delaying the progression of kidney disease.The FIDELIO-DKD study has demonstrated a significant decrease in the risk of renal composite endpoint events in patients with T2DM and CKD treated with finerenone. 166The results from the Chinese subgroup data are consistent with TA B L E 5 Risk of CKD progression and visit frequency, classified by eGFR and UACR.those in the overall population. 167The FIDELITY study, a predefined pooled analysis of two large international multicenter phase III trials (FIDELIO-DKD and FIGARO-DKD 168 ), has revealed that finerenone significantly decreases the long-term risk of renal and cardiac composite events in older individuals with T2DM and CKD, in agreement with findings in the overall population. 169For older patients with diabetes with CKD and proteinuria (eGFR ≥25 mL min −1 (1.73 m 2 ) −1 ), adding finerenone to the maximum tolerated dose of ACEI or ARB is recommended to decrease proteinuria and delay CKD progression.Monitoring of serum potassium and renal function is essential.Additionally, a few cases of severe anemia have been reported.
4. Smoking should be ceased, and blood lipid and uric acid levels should be controlled.

Collaborative multidisciplinary management with a nephrologist
is recommended for older patients with diabetes with combined CKD.
6. Drugs should be used with caution, unnecessary use of Chinese and Western medicines should be avoided, and patients should particularly be warned not to use so-called kidney-protecting drugs.

| Diabetic eye diseases
Diabetes is associated with a variety of eye diseases.Diabetic eye diseases may cause visual acuity decrease or even blindness and may make older people with diabetes unable to participate in social activities; compromise their capability of fingertip pricking for glucose measurement and insulin injection; and increase their risk of  ing macular edema involving the central fovea. 173

| Other related eye diseases
T2DM is a risk factor for cataracts. 174Age is closely associated with cataracts, and cataracts are the main cause of blindness in older people. 175aucoma is the second leading cause of blindness in older people, and people with diabetes have a higher risk of glaucoma than those without diabetes. 176Examining visual acuity and intraocular pressure and screening for cataracts and glaucoma are particularly important in older patients with diabetes.Beyond eye disease that may decrease visual acuity, attention should also be paid to xerophthalmia in older people with diabetes.
Xerophthalmia is the most prevalent ocular surface disease. 177Diabetes is significantly associated with the risk of xerophthalmia. 178A communitybased study in Shanghai has indicated a 17.5% prevalence of xerophthalmia in patients with T2DM with a mean age of 69 years. 179Xerophthalmia can lead to a variety of eye discomforts (e.g., dry eye, eye redness, sensation of sand or gravel in the eyes, burning sensation, foreign body sensation, excessive tearing, and photophobia) and visual impairment, 180 and may contribute to decreased sleep quality, as well as the development of anxiety and depression. 181Older patients with diabetes should be asked about the presence of xerophthalmia symptoms, and further examinations and initiation of treatments should be performed if necessary.

| Diabetic neuropathy
Diabetic neuropathy, a common chronic complication of diabetes, is heterogeneous, affecting different central and peripheral nerves, and presenting as diverse clinical manifestations.DSPN is the most representative diabetic peripheral neuropathy.Beyond DSPN, DAN is also a common diabetic peripheral neuropathy.DAN can involve multiple systems, including the cardiovascular, gastrointestinal, urogenital, and sudomotor systems, thus resulting in an array of symptoms and signs, such as hypoglycemia unawareness, tachycardia at rest, postural hypotension, gastroparesis, constipation, diarrhea, erectile dysfunction, neurogenic bladder, and sweating disorders, among which CAN is the greatest concern.Independently of other cardiovascular risk factors, CAN is associated with mortality risk. 182 addition, gastrointestinal autonomic neuropathy manifests as symptoms including dysphagia, hiccups, gastroparesis, constipation, and diarrhea, which severely affect quality of life in older people with diabetes.

| DSPN
DSPN, the most common diabetic neuropathies type, accounting for approximately 75% of cases, is an important risk factor for diabetic foot ulcers and is also a major contributor to falls and fractures. 183e is an independent risk factor for DSPN, 184  patients with T2DM. 186The overall prevalence of CAN in T2DM is as high as 62.6%, and that in patients with T2DM ≥ 60 years of age is 67.5%, a value slightly higher than that in the general population.
Multifactorial logistic regression analysis has identified age as an independent risk factor for CAN. 187For older patients with diabetes,  pain, with combination therapy being superior to monotherapy. 192cause of the substantial incidence of adverse reactions associated with TCA medications, attention should be paid when these drugs are used in older patients with diabetes.

| Lower extremity arterial disease and diabetic foot
Lower extremity arterial disease (LEAD) is a peripheral arterial disease manifested as stenosis or occlusion of the lower extremity arteries.Normally, LEAD in patients with diabetes refers to lower extremity atherosclerotic disease.According to the China DIA-LEAD study, the overall prevalence of LEAD in patients with T2DM 50 years or older in China is 21.2%, and the prevalence increases with age and the course of diabetes. 193In patients with T2DM with LEAD, age is independently associated with lesion severity. 194The risks of death due to myocardial infarction, stroke, and coronary heart disease are all elevated in patients with LEAD. 195LEAD is also a major risk factor for diabetic foot.Vasodilators such as cilostazol, sarpogrelate, pentoxifylline, and prostaglandins can ameliorate ischemic symptoms in the lower limbs; however, for patients with LEAD who do not respond to medical treatment, experience severe intermittent claudication affecting the quality of life, or have skin ulcers or gangrene, revascularization may be considered appropriate to maintain their functional status and independent ADL.Therefore, these individuals have elevated risk of diabetic foot, and make up most of the population with diabetic foot in China. 197e management of diabetic foot emphasizes that prevention is

| Hypoglycemia
In older patients with diabetes, hypoglycemia is one of the common acute complications, resulting in arrhythmia, myocardial infarction, falls, and even coma, death, and other adverse events.Repeated episodes of severe hypoglycemia can cause cognitive decline and even dementia in these patients. 201 Define and standard: Currently, both domestic and international guidelines define and classify hypoglycemia as follows: For diabetes patients undergoing drug treatment, blood glucose levels below 3.9 mmol L −1 are considered hypoglycemic.( 1) Grade 1 hypoglycemia: Blood glucose <3.9 mmol L −1 and ≥3.0 mmol L −1 .
(2) Grade 2 hypoglycemia: Blood glucose <3.0 mmol L −1 .(3) Grade 3 hypoglycemia: Severe events requiring assistance from others, accompanied by changes in consciousness and/ or body, but without specific blood glucose limits. 202Due to the strong heterogeneity of the elderly population and the lack of hypoglycemia studies specifically in this group, coupled with the absence of unified diagnostic criteria for hypoglycemia in different studies, there is a lack of large-scale epidemiological data on the incidence of hypoglycemia in elderly diabetes patients in China.
2. Risk factor: Age is one of the risk factors for hypoglycemia 203 ; the risk of hypoglycemia is higher in older patients with diabetes than in non-elderly ones. 204In addition to the age actor, compromised ability of glucose regulation, multiple concurrent diseases (e.g., CKD, cardiovascular disease, hepatic insufficiency, etc.), polypharmacy, and concurrent autonomic neuropathy are all risk factors for hypoglycemia in older patients with diabetes. 205Cognitive decline is also an important contributor to the increased risk of severe hypoglycemia in older patients with diabetes. 206Unhealthy living habits such as fasting alcohol consumption, excessive carbohydrate restriction, irregular eating, and no extra meals before heavy exercise are common triggers for hypoglycemia.patients, these patients are at higher risk of asymptomatic hypoglycemia, and the risk of severe hypoglycemia and even death is higher in older patients with diabetes who have asymptomatic hypoglycemia. 208Repeated episodes of hypoglycemia may further decrease the neurological responses, 209 and patients may even experience coma directly in the absence of sympathetic activation. 210The above conditions, if occurring in the nighttime, are extremely dangerous because it is difficult to identify and timely treat the disorders.
4. Prevention and treatment: It should be particularly highlighted that improper use of insulin and secretogogue is an important contributor to hypoglycemia in older patients with diabetes. 211erefore, insulin, sulphonylurea secretogogues, glinide secretogogues, and other glucose-lowering medications at high risk of hypoglycemia should be used with caution.If such drugs are used, blood glucose monitoring should be strengthened, and if necessary, the CGM can be applied. 212Single-agent use of metformin, DDP-4 inhibitors, alpha-glucosidase inhibitors, GLP-1RAs, and SGLT2 inhibitors is associated with a lower hypoglycemia risk. 213However, because older patients with diabetes often have multiple concurrent diseases, caution should still be exercised when using these drugs to avoid an increased risk of hypoglycemia due to potential interactions with other medications. 214An increased hypoglycemia risk is associated with strict glycemic control. 215Therefore, it is crucial to set reasonable HbA 1c targets tailored to individual patient circumstances in elderly diabetic patients to reduce the occurrence of hypoglycemia.When setting personalized HbA 1c targets, careful consideration should be given to several factors, including the duration of diabetes, the patient's life expectancy, the use of insulin and secretagogues, history of severe hypoglycemia, and the presence of other conditions (such as multiple comorbidities, cognitive impairment, polypharmacy). 216Older patients with T1DM have a high incidence of severe hypoglycemia, especially those with a prolonged disease course. 217sults from RCTs suggest that CGM may contribute to reducing the risk of hypoglycemia in elderly T1DM patients, 218 and its use should be considered for eligible patients when necessary.

| Hyperglycemic crisis
Hyperglycemic crises mainly include hyperglycemia hyperosmolar state (HHS) and diabetic ketoacidosis (DKA).HHS is one of the severe acute complications of diabetes, clinically characterized by severe hyperglycemia, elevated plasma osmolarity, dehydration, and altered consciousness, usually without obvious ketosis and metabolic acidosis.Older patients with diabetes are the main population affected by HHS.HHS has a higher mortality rate than DKA, approximately 10 times higher, 219 and requires high attention from clinicians.Infection is the primary trigger for HHS, followed by inappropriate discontinuation of hypoglycemic agents such as insulin, or the presence of other concurrent diseases such as myocardial infarction, cerebrovascular events, and trauma. 220The onset of HHS is latent, with 30% to 40% of HHS patients never diagnosed with diabetes before.Although DKA is not common in older patients with diabetes, a variety of complications and comorbidity are more likely to occur in these patients than in non-elderly ones, causing organ and system dysfunctions, and ultimately resulting in poor outcomes. 221It should be noted that co-existence of DKA and HHS is not rare.In recent years, with the use of immune checkpoint inhibitors, diabetes onset following the use of these inhibitors is often characterized by the onset of DKA 222 and may also be accompanied by HHS. 223Therefore, older patients with diabetes using immune checkpoint inhibitors should be vigilant for both DKA and HHS.Older patients with diabetes using SGLT-2 inhibitors should also be aware of the potential occurrence of DKA. 224dominal pain, nausea, and vomiting are common clinical manifestations of DKA, with neurological symptoms being more prominent in elderly diabetes patients experiencing DKA, while gastrointestinal symptoms may be less apparent.The diagnostic points include: blood glucose increased, blood ketone bodies and /or urine ketone bodies increased, as well as blood PH value and/or carbon dioxide combining power decreased.Regardless of DKA or HHS alone, or both, the treatment should adhere to the following principles: initiate fluid replacement as soon as possible to restore the blood volume, lower blood glucose and correct electrolyte and acid-base imbalances, and meanwhile actively look for and remove the cause, prevent complications, and reduce mortality.

| Lactic acidosis
Although rare, lactic acidosis is highly fatal and extremely dangerous.In diabetic patients, renal insufficiency may cause accumulation of biguanides in the body, increasing the risk of lactic acidosis.Older patients with diabetes who have hepatic/renal insufficiency should be alert to lactic acidosis when using biguanides.

| Heart failure
Both age and diabetes are risk factors for heart failure, and the prevalence of heart rate is up to 22.3% in older patients with diabetes. 225 recent years, foreign single-center studies have shown that the prevalence of heart failure in hospitalized elderly diabetic patients is even as high as 56%. 226Heart failure with preserved ejection fraction (HFpEF) is more common in elderly diabetic patients, which is prone to be underdiagnosed.Studies have shown that heart failure is missed in up to 27.7% of elderly diabetic patients. 227Heart failure is independently associated with cardiovascular death and hospitalization risk. 228though heart failure is common in older patients with diabetes, there is lack of clinical evidence required for developing the best treatment strategy.Insulin may exacerbate heart failure by causing water-sodium retention and thereby should be used with caution in older patients with diabetes and concurrent heart failure.TZDs are contraindicated in older patients with diabetes who are rated as New York Heart Association functional class III or higher.In the SAVOR study, the rate of hospitalization for heart failure as one of the components of the secondary endpoints was elevated in the saxagliptin-treated group compared to the placebo group, 229 and saxagliptin should be used with caution when selecting a DPP-4 inhibitor for older patients with diabetes with heart failure.Metformin is safe and beneficial in patients with diabetes and heart failure 230,231 and should be retained in the treatment regimen if there are no contraindications or intolerance.SGLT-2 inhibitors can reduce the risk of hospitalization for heart failure, and the results were similar in the elderly subgroup to the overall population. 73This class of drug should be preferred in elderly diabetic patients with comorbid heart failure. 232Cohort studies have shown that GLP-1RAs also improve composite endpoints including hospitalization for heart failure compared to DPP-4 inhibitors.

| Osteoporosis
Osteoporosis is an aging-related disease, with a significantly higher prevalence of osteoporosis in people aged 60 years and above, and the prevalence of vertebral fractures in women aged 80 years and above can be as high as 36.6%. 234The risk of fracture in patients with diabete significantly exceeds that of the non-diabetic population. 235Data from Beijing showed that the prevalence of diabetes with osteoporosis was 13.4% to 14.8% from 2016 to 2018, and the prevalence of osteoporosis in older patients with diabetes was higher than that in young patients with diabetes. 236Therefore, older patients with diabetes are a high-risk group for osteoporotic fractures, and once fractures occur in older adults with diabetes, the quality of life is seriously affected, with high rates of disability and mortality.Fall history, fracture history, low grip strength, and elevated HbA 1c are risk factors for fractures in older T2DM patients. 237BMD measurement by dual-energy X-ray absorptiometry and the fracture risk assessment tool FRAX can be used to assess the fracture risk of diabetic patients but may underestimate such risk.T2DM is more prone to fracture than non-diabetic population at the same BMD. 238The fracture risk assessment tool, FRAX, similarly underestimates fracture risk in diabetic patients. 239Education on osteoporosis prevention and treatment in older patients with diabetes should be strengthened, with active assessment of fracture risk and early intervention.Older patients with diabetes with osteoporosis should be cautious about using glucose-lowering medications that may increase the risk of osteoporosis or fractures.The Chinese expert consensus recommends that the management of diabetes mellitus combined with osteoporosis refer to non-diabetic patients. 240lti-disease coexistence and multiple medications need to be considered in the selection of osteoporosis medications, and individualized medications and monitoring should be performed after a thorough assessment and weighing of the pros and cons.

| Sarcopenia and frailty
Geriatric syndromes are a cluster of multiple abnormalities prevalent among older adults, which severely affect their quality of life and lead to poor clinical outcomes.The Asia-Pacific consensus states that geriatric syndromes should include Alzheimer's disease, pressure sores, hearing loss, visual loss, sarcopenia, frailty, and fall, etc. 241 Compared to non-diabetic older people, older patients with diabetes have a higher prevalence of geriatric syndromes.
Sarcopenia is an aging-related disease with a prevalence of 14.8% in older patients with diabetes in China. 242T2DM is associated with decreased muscle strength and poor muscle mass, exacerbating agerelated sarcopenia. 243T1DM can also develop sarcopenia, 244 the pathogenesis of which is related to autoimmune damage. 245Diabetic patients with sarcopenia have more severe abnormalities of glucose metabolism, poorer nutritional status, and are also more likely to have comorbid osteoporosis and falls. 246Sarcopenia makes it more difficult for older patients with diabetes to control their blood glucose, reduces the ADLs, and increases mortality. 247Therefore, sarcopenia in geriatric diabetes should be emphasized.Due to changes in body composition associated with increased age, older patients with diabetes can develop both obesity and sarcopenia, that is, sarcopenic obesity. 248The prevalence of sarcopenic obesity increases with age, reaching 48.0% in women and 27.5% in men over 80 years of age. 249rcopenia in obese older patients with diabetes should not be ignored to avoid mindless weight loss and medication-induced underweight.It is recommended to assess older patients with diabetes for sarcopenia according to the screening and diagnostic criteria of the Asian Working Group for Sarcopenia. 250In the community primary Frailty refers to a pre-disability state in which the body becomes more and more vulnerable with age due to degenerative changes, physiological reserve function decline and various chronic diseases, and subsequently loses its ability to resist physical or mental stress.
Therefore, unlike disability and co-morbidity, the cause of frailty is somewhat reversible, and the prognosis of older people with frailty can be improved by early identification and intervention.In the elderly, diabetes increases the risk of frailty fivefold, 251 leading to reduced mobility, increased difficulty in monitoring and managing blood glucose, and affecting patient prognosis.A meta-analysis showed that the prevalence of frailty and pre-frailty among community-dwelling older patients with diabetes was 20.1% and 49.1%, respectively. 252e degree of frailty of the patient needs to be taken into account when setting goals for glycemic control, and simplification, switching, or downgrading of treatment regimens may be necessary in older diabetic patients with comorbid frailty, with particular consideration given to the reduction of treatments that may induce hypoglycemia, such as sulfonylureas and insulin. 253Meta-analysis revealed that the use of sulfonylureas in older adults with T2DM may increase the risk of fracture, which may be linked to their triggering of hypoglycemia. 254ncerns and assessment of sarcopenia and frailty in older patients with diabetes and making appropriate interventions can help to improve the prognosis and reduce health care expenditures. 255,256

| Falls
Falls are the leading cause of traumatic fractures and injury-related deaths in Chinese elderly population.As people age, they are at increased risk of falls due to the decline in various physiological functions, including decreased gait coordination and balance resulting from functional decline in the maintenance of the musculoskeletal motor system, as well as declines in vision, hearing, vestibular function, and proprioception.Diabetes increases the risk of falls in the elderly, especially those on insulin, where the risk of falls is 94% higher than in non-diabetic elderly. 257Falls, while high among older patients with diabetes, are preventable.All older patients with diabetes need to be assessed for fall risk, including past medical history, somatic functional status, environment, and psychological assessment.Major risk factors for falls in older patients with diabetes include hypoglycemia and glucose fluctuations, central and peripheral neuropathy, vascular factors, orthostatic hypotension, postprandial hypotension, diabetic ophthalmopathy, medications (antihypertensives, diuretics, sedative-hypnotics, etc.), and sarcopenia and frailty.
For older patients with diabetes who have the above-mentioned conditions, physicians should provide active intervention and seek assistance from relevant departments to reduce the risk of fracture and fracture-related complications in such patients.Be cautious of falls in older patients with diabetes with comorbid osteoporosis.

| Cognitive dysfunction
The prevalence of cognitive dysfunction among older patients with diabetes in China is 48%, with higher prevalence among women, older age, lower education level, lower income, no spouse, and living alone. 258There is a bidirectional relationship between cognitive dysfunction and risk of hypoglycemia. 259,260Hypoglycemia increases the risk of developing dementia, including vascular dementia and A retrospective study showed that metformin was significantly associated with a reduced risk of dementia and showed a dose-dependent effect in older patients with T2DM. 264GLP-1RAs are associated with a reduced incidence of Alzheimer's disease in elderly patients. 265The on cognitive function are unclear. 266Exercise also helps to improve cognitive function, and a randomized clinical trial found that tai chi was more effective than fitness walking in improving cognitive function in Chinese older patients with T2DM. 267

| Mental illness
The risk of depression is higher in older patients with diabetes than in non-diabetic older adults 268 but is easily overlooked.Depression and anxiety may lead to less adherence in older patients with diabetes and less effective glycemic control. 269Attention should be paid to the mental status of older patients with diabetes for early identification of psychiatric disorders and intervention.Simplified screening tools such as the Geriatric Depression Scale can be used for early identification.A multidisciplinary collaborative care pattern can be established and perfected to improve patients' depression and anxiety symptoms, which will not only improve the quality of life, but also facilitate glycemic control.Delirium is often seen in the elderly population. 270If delirium occurs in older patients with diabetes, timely identification and removal of triggers, active encouragement of family members to participate in the process of non-pharmacological treatment, and nursing support are helping to prevent and treat delirium-related complications.

| Hypotension
Aging leads to changes in cardiovascular structure and function; therefore, older adults are prone to orthostatic and postprandial hypotension. 271Hypotension increases the risk of falls 272 and even increases the risk of cardiovascular events and death. 273,274Older patients with diabetes are at higher risk of orthostatic hypotension than non-diabetic elderly, and 40% of orthostatic hypotension patients have comorbid diabetes. 275Older patients with diabetes with hypertension may have concomitant orthostatic hypotension; therefore, ARBs or calcium channel blockers should be preferred in this group of patients, 276,277 and antihypertensive medications such as tamsulosin and carvedilol, which may worsen orthostatic hypotension, should be avoided.
In the elderly, intake of carbohydrate-rich hot food and upright posture are both associated with symptomatic postprandial hypotension. 278e association of symptoms such as dizziness and syncope with eating and postural changes should be addressed in older diabetic patients.
Lifestyle modifications may reduce symptomatic hypotension in older patients with diabetes.In addition, α-glucosidase inhibitors help to improve the symptoms of postprandial hypotension in older patients with diabetes 50,279 and should be considered when selecting hypoglycemic agents.
SGLT-2 inhibitors have a mild blood pressure lowering effect and should be of concern in patients applying this class of hypoglycemic agents.

| Tumors
Patients with diabetes have an increased risk of tumors, including hepatocellular carcinoma, hepatobiliary carcinoma, pancreatic cancer, breast cancer, ovarian cancer, endometrial cancer, and gastrointestinal malignancies. 280,281It is recommended that older patients with diabetes get tumor screening matched to their age and gender.
As elevated blood glucose is sometimes the first clinical manifestation of pancreatic cancer, 17 284 and obesity is also an important risk factor for OSAS.OSAS is usually more severe in those with diabetes 285 and closely associated with the occurrence and progression of diabetic complications.The prevalence of OSAS is higher in men than in women, and obviously higher in postmenopausal women than in premenopausal ones.It is recommended that obese older patients with diabetes be routinely screened for OSAS.
For older patients with diabetes with OSAS, active lifestyle interventions for weight loss, smoking cessation, alcohol restriction, and avoiding strong tea and coffee, as well as daytime overexertion and excitement that affects sleep, should be carried out. 286CPAP, an effective treatment for OSAS, can significantly improve the blood glucose level and insulin resistance of diabetic patients. 287,288  Itchy skin is a common symptom in diabetic patients, with 12.7% of T2DM patients experiencing itchy skin, and the incidence of itchy skin is even higher in T2DM with comorbid diabetic peripheral neuropathy (20.5%). 296Advanced age and long disease duration are also risk factors for pruritus. 297 in dosage; co-administration with carbamazepine accelerates its metabolism, significantly reducing its hypoglycemic effect. 298Vildagliptin used in combination with ACEIs may increase the risk of angioneurotic edema. 299Rosiglitazone and pioglitazone are metabolized by CYP2C8, and drugs like gemfibrozil and clopidogrel slow down their metabolism, increasing plasma drug levels 300 ; inducers of CYP2C8 such as rifampin accelerate drug metabolism, reducing their efficacy.Therefore, the drug use profile of older patients should be a factor to consider when developing the drug therapy regimen, and for patients with polypharmacy, glucose-lowering medications with less drug interactions should be chosen to avoid drug-drug interactions.

| Nursing home management of diabetes in the older patients
With the accelerated progress of the aging of population in China, the health management of older patients with diabetes in nursing home has become increasingly important.For nursing homes with HCPs, older patients with diabetes can be managed by referring to hospital management mentioned above.However, at present, nursing homes in China mainly provide basic life care, lacking health management services for chronic diseases such as diabetes.It is necessary to strengthen education on diabetes for caregivers. 136Overly stringent dietary control provides limited help for the glycemic control of older patients with diabetes 303 and may increase the risk of malnutrition.In setting glycemic management goals, it is crucial to fully consider the complications and comorbidities, functional status, and life expectancy of the older patients. 304Dietary and exercise plans should be formulated according to different overall health status, glycemic control, and complication status.Currently, the portable glucosemeters are commonly employed in nursing homes HbA 1c testing and continuous glucose monitoring (CGM) may also be conducted in some nursing homes.For older patients treated with sulfonylurea drugs or insulin, the use of CGM to assess the risk of hypoglycemia may be considered. 136It is imperative to promptly identify acute diabetic complications in older patients; and suspected cases of diabetic ketoacidosis (DKA) and/or hyperosmolar hyperglycemic state (HHS) should be urgently managed and immediately transferred. 304Attention should be given to foot care in older patients with diabetes, and those with any skin ulceration of the feet should be referred promptly to an endocrinologist or a department related to diabetic foot disorders.

| Home management of diabetes in the older patients
Diabetes is highly prevalent in the elderly living at home, 305 being one of the chronic diseases requiring great concern from them.The home management of older patients with diabetes should include the selfmanagement of the patients living at home and their family member's care, as well as chronic disease management carried out by community health care institutions.The multidisciplinary team intervention pattern can optimize the blood glucose and mindset of these patients and increase their self-management ability to a certain extent. 306The home management of older patients with diabetes should pay attention to preventing acute events such as hypoglycemia, hyperglycemic crisis, and falls, etc.

| Perioperative management
The perioperative glycemic goal of older patients with diabetes is from 7.8 to 10.0 mmol L −1 . 108,307For older patients with severe comorbidities and frequent events of hypoglycemia, the control target can be as high as 13.9 mmol L −1 . 307For patients who plan to receive cardiac operation or other sophisticated surgeries, it is suggested to consider a more stringent glycemic goal, i.e., from 6.1 to 7.8 mmol L −1 , with the hypoglycemia risk considered. 308To minimize the impact of blood glucose, patients with diabetes are preferably operated on in the early morning or as early as possible.Patients with later surgery times should have their blood glucose continuously monitored in the ward. 309Fasting is required for surgery, all oral glucose-lowering medications (OGLMs) should be discontinued on the morning of the operation day, and blood glucose monitoring should be carried out once every 4-6 hours during the fasting period.During the surgery, the frequency of blood glucose monitoring should be increased according to the patient's condition; when the blood glucose level is beyond the control goal, short-acting human insulin or rapid-acting insulin analogue should be given.For patients undergoing minor surgery whose blood glucose can be controlled well by OGLMs, it is not necessary to use insulin during the surgery, but their OGLMs should be resumed after surgery.During fasting, attention should be paid to discontinuing medications with a high risk of hypoglycemia, and the use of SGLT-2 inhibitors should be suspended during surgery to avoid the risk of DKA. 309For patients undergoing major and intermediate surgeries, especially those with suboptimal glycemic control, it should be switched to insulin therapy in a timely manner, and during the surgery, insulin therapy should be continued with close monitoring of blood glucose.Intravenous infusion of insulin may be given to control blood glucose before restoration of normal diet after surgery, and switched to subcutaneous injection after normal diet is restored.For patients who plan to receive an emergency surgery, too stringent glycemic goals should be avoided before surgery, pre-procedure preparation should be completed as soon as possible, and their blood glucose should be lowered by intravenous infusion of insulin and monitored during the surgery.During the perioperative period, attention should be paid to monitoring fluctuations of blood glucose and watching out for hypoglycemia.

| Infection and vaccination
Patients with diabetes are susceptible to concurrent infections with bacteria, fungi, viruses, and atypical pathogens, with the common sites including the respiratory system, urinary system, skin, and soft tissues.Compared to the general population, patients with T2DM have a worse prognosis upon infection, with higher rates of incidence and mortality from sepsis. 310tients with diabetes are at a greater risk of skin and soft tissue infections (SSTIs) than non-diabetic patients, yet patients with severe diabetic neuropathy and vasculopathy may not exhibit typical SSTI symptoms. 311Infections are highly prevalent and not easy to be controlled in older patients with diabetes. 312A retrospective cohort study showed that compared to patients with diabetes aged 40 to 49 years, the risk of hospitalization was 3 to 4 times higher in patients aged 80 to 89 years, with a high proportion of infection-related hospitalizations. 313 Therefore, for the long-term management of acute COVID-19 infections and persistent symptoms (i.e., long COVID) in patients with diabetes, the use of glucose-lowering medications that do not increase body weight and improve cardiorenal outcomes (such as SGLT-2 inhibitors and GLP-1RAs) is recommended, although there is no evidence from long-term follow-up. 315od glycemic control enhanced personal hygiene management, and necessary vaccination can prevent serious infections to a certain extent.Older patients with diabetes should receive influenza and pneumococcal vaccines based on individual conditions to reduce their hospitalization and death risks.However, the live attenuated vaccines should be avoided for the influenza vaccination. 316r older patients with diabetes comorbid with infection, stringent glycemic control is the primary measure; however, for those with multiple concurrent diseases and a short life expectancy, the glycemic goals can be approximately relaxed while effective anti-infective therapy is given, and surgical therapy should be administered as needed.that carry a risk of hypoglycemia, allowing blood glucose levels to remain at the upper limit of normal range or within the acceptable range in which acute metabolic abnormalities are absent.Medication can be discontinued when necessary, taking the amount of food intake into account.In the case of patients with organ failure, the insulin dosage for T1DM patients can be reduced in correspondence with decreased food intake but should not be completely discontinued.There is no definitive consensus on the treatment approach for T1DM patients in a terminal state; however, low dose of basal insulin may be used to prevent acute complications from hyperglycemia.Similar to the management of T2DM in the elderly, glycemic goals and glucose-lowering regimen should be developed for older patients with T1DM based on their age, life expectancy, functional status, underlying diseases, and complication profile, etc. Due to difficulties in blood glucose management, the risks of hyperglycemic crisis and hypoglycemia are higher in older patients with T1DM than in older patients with T2DM.Before the occurrence of microvascular or macrovascular complications, more stringent glycemic goals may be considered for older patients with T1DM, but the hypoglycemia risk must be weighed.Long course of disease is a risk factor for hypoglycemia in older patients with T1DM, and the incidence of severe hypoglycemia is up to 18.6% in older patients with T1DM >40 years, 217 for whom the glycemic goals should be appropriately relaxed.
In recent years, there have been significant advancements in diabetes management technology, particularly in the fields of insulin injection and blood glucose monitoring.Studies focusing on older patients with T1DM have shown that those using CGM or insulin pumps have lower levels of HbA 1c , fewer hypoglycemic events, and less glycemic variability. 318The WISDM randomized clinical trial indicated that CGM used in older patients with T1DM can reduce the occurrence of hypoglycemia and improve overall glycemic control compared to fingerstick blood glucose monitoring. 319Furthermore, research has confirmed the safety of hybrid closed-loop insulin pumps in older patients with T1DM.
Compared with the sensor-augmented pump (SAP) group, the hybrid closed-loop group had higher Time-in-Range (TIR) and lower Time-Below-Range (TBR). 320It should be noted that the afore- HbA 1c is clinically used as the gold standard for evaluating longterm glycemic control and an important basis for adjustment of treatment regimen.For patients who have not achieved the HbA 1c goal, it is suggested to test HbA 1c once every 3 months.Once the goal is achieved, HbA 1c can be tested once every 6 to 12 months.However, HbA 1c also has certain limitations; for example, it cannot reflect blood sugar fluctuations or capture hypoglycemic events.It is suggested that older patients with diabetes on insulin therapy should carry out self-monitoring of blood glucose primarily while fasting and before meals, to find out their baseline blood glucose levels; for those at risk of nocturnal hypoglycemia, it is suggested to monitor bedtime and nighttime blood glucose levels additionally based on the patient's condition; however, for those whose blood glucose is controlled stably by OGLMs, frequent monitoring is not required.

Key points
1. HbA 1c should be tested once every 3 months before the goal is achieved and once every 6 to 12 months after the goal is achieved; for patients on insulin therapy or at high risk of hypoglycemia, self-monitoring of blood glucose In older patients with CGM can further improve HbA 1c and meanwhile reduce glycemic variability, without increasing the hypoglycemia risk. 321,322Due to poor pancreatic islet function and great glycemic variability, T1DM patients are more likely to benefit from CGM.It is suggested that clinicians make suggestions on whether to wear CGM after comprehensive assessments based on the patient's blood glucose condition, cognitive level, mobility, economic condition, etc.Among older T2DM patients using basal insulin, those using CGM show an increase in TIR compared to patients using blood glucose monitoring, with benefits consistent with younger patients. 323R refers to the length of time in 24 h that glucose is in the target range or the percentage of the target range.Normally, the blood glucose range of TIR in adult patients with diabetes is defined as 3.9-10.0mmol L −1 , but there is still lack of studies on TIR in older patients with diabetes.In recent years, international consensus recommends that TIR can be used as a measure for evaluating the glycemic control condition of adult patients with T1DM and T2DM, and TBR and TAR can also be used as parameters for evaluating the efficacy of treatment regimen.Studies in China have shown that, in T2DM patients, TIR is independent of HbA 1c but associated with microvascular complications of diabetes (mean age of patients: 60.4 years) 324 and related to cardiovascular and all-cause death (mean age of patients: 61.7 years). 325In the management of older patients with diabetes, TIR can also be used as a supplementary target for evaluating the glycemic control level, but such use remains to be supported by studies in older patients with diabetes.The definition of TIR goal should consider the individual differences and hypoglycemia risk of older patients with diabetes and needs support from further evidence-based medical proofs.Research show a strong correlation between TIR and TAR in T1DM, but a weak correlation with TBR.For older patients using automated insulin delivery systems, prioritizing the reduction of TBR is recommended to decrease the risk of hypoglycemia. 326In addition to affecting glycemic control, CGM offers other benefits for older diabetes patients, such as continuous sharing of glucose results with family or caregivers, reducing the need for fingerstick glucose testing, especially for patients with physical disabilities, cognitive impairments, or visual impairments.For patients with reduced or impaired hypoglycemia awareness, CGM can help them detect low blood sugar episodes.proving patient compliance and enhancing blood glucose control. 332 addition, needle-free injection can reduce adverse reactions associated with needle injections, such as subcutaneous nodules, fat hypertrophy, or atrophy, and reduce insulin dosage.It can be used conditionally for older diabetes patients in good (Group 1) and intermediate (Group 2) health.However, needle-free injection is more complicated than insulin pen injection and it is necessary to be instructed by professional personnel and master the operation method before self-injection.Patients who cannot self-administer injections should be educated to actively assist by family members or consider alternative injection methods.

| Insulin pump
Insulin pump is an insulin delivery device controlled by artificial intelligence.It can carry out continuous subcutaneous insulin injection and maximally simulate the physiological secretion of insulin to facilitate blood glucose management.For older patients with diabetes, especially T1DM, if multi-dose subcutaneous insulin injection therapy is associated with great glycemic variability and high hypoglycemia risk, insulin pump will be suggested.Patients who struggle with the precise adjustment of insulin dosage with multiple subcutaneous insulin injections may also consider the application of an insulin pump.Research suggests that in older T2DM patients, compared to multiple insulin injections, the use of an insulin pump effectively controls blood glucose with good safety and patient satisfaction. 333udies confirm the safety and efficacy of the automatic insulin delivery system in T2DM patients with an average age exceeding Cognitive decline, visual acuity finger dexterity decrease, lack of assistance from others, and lack of insulin pump knowledge may all be factors that limit the use of insulin pump in older patients with diabetes. 335Clinicians should determine whether to adopt insulin pump therapy based on patients' individual condition and adequately educate patients and their families on knowledge about insulin pump, including the setting of insulin pump, how to handle alarms, and potential complications, etc.A good assistance pattern should be established to handle the requirement rapidly and effectively for insulin pump adjustment, so as to avoid insulin pump-related acute adverse events.

| CHAP TER 17: D IAB E TE S IN THE OLDER PATIENTS AND TR ADITIONAL CHINE S E MED I CINE ( TCM)
In Chinese medicine, diabetes belongs to the category of "Xiaoke disease (disease with symptoms of frequent drinking and urination)" and has a long history of traditional medical treatment in China.
According to TCM, its basic pathogenesis is "Yin deficiency and dryness-heat" and involving diseases in the lungs, stomach, kidneys, individual is unable to perform an activity independently and requires assistance from others, it is to be considered as one impairment.The total number of impairments is calculated accordingly).

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IADL Scale.

Mode of transportation
Guideline for the Management of Diabetes Mellitus in the Elderly inChina (2021 Edition) and released the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition).
Since the release of the previous version of the guideline, additional relevant research on older people with diabetes has been reported.Therefore, the Expert Committee organized an update of the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition) and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition).The English literature search on which the guideline was based was performed in PubMed, Web of Science, Scopus, Ovid, Cochrane Library databases, the National Institute for Health and Care Excellence (NICE), the Registered Nurses' Association of Ontario (RNAO), the National Guideline Clearinghouse (NGC), the Scottish Intercollegiate Guidelines Network (SIGN), the Joanna Briggs Institute (JBI) Library, the British Medical Journal (BMJ) Best Practice, and other guideline libraries.The Chinese literature search included literature in the China Biology Medicine disc, China National Knowledge Infrastructure, WANFANG DATA, and VIP China Science and Technology Journal Database.The inclusion criteria for literature were as follows: (1) studies of patients 65 years or older and (2) literature types of clinical guidelines, systematic reviews, meta-analyses, randomized control trials (RCTs), cohort studies, cross-sectional studies, case-control studies, expert consensus, etc.Evidence in the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition) is rated as level A, B, or C. Level

Key points 1 .
The World Health Organization (WHO) diagnostic criteria for diabetes (1999) are used.(A) 2. Diabetes in older people can be classified into type 1 diabetes mellitus (T1DM), T2DM, and special types of diabetes.(A) 3. Diabetes in older people has unique characteristics, including atypical symptoms, multiple complications and/ or concurrent diseases, etc. (B) 4. Tumor screening is recommended for newly diagnosed older patients with diabetes.(C)

3 .
A stratified, individualized integrated treatment, nursing, and rehabilitation strategy is developed according to patient health status.(A) TA B L E 1 Diagnostic criteria for diabetes in older people.

8 | 5 1 ) 5 2 points 1 . 2 .
a result, individualized health education should be carried out according to the characteristics of each patient.Older patients need to be assessed before health education is carried out, including basic information, education level, economic status, previous treatment status, blood glucose level, comorbidities, cognitive function, and the presence of caregivers.The contents of education should cover the etiology, disease progression and clinical manifestations of diabetes, hazards of diabetes, identification and treatment of acute and chronic complications of diabetes, goal of individualized treatment, lifestyle intervention, characteristics of various kinds of drugs, choice and use of clinical drugs, and how to carry out blood glucose monitoring, etc. Health education on patients themselves, family members and caregivers, and community-related personnel should be strengthened to enable them to have a correct understanding of disease-related knowledge and to avoid excessively aggressive or relaxed blood glucose management, thus improving the quality of life of older patients with diabetes.Diabetes education can be carried out in the forms of collective education and more targeted community group education, peer education, and individual education.If possible, remote education via WeChat public account, mobile app, and online training course, etc., can also be adopted.These methods can be carried out simultaneously to complement each other, to better pass on the necessary information to patients.In recent years, there have been numerous studies exploring different educational approaches for older patients with diabetes, such as the spousal-assisted management model and the PRECEDE-PROCEED model. 25,26Effective educational approaches will contribute to the comprehensive management of older patients with diabetes.With the rapid development of artificial intelligence technology, recent years, there have also been several studies investigating the role of artificial intelligence in diabetes education. 27CHAP TER 6: G LYCEMIC G OAL S FOR OLDER PATIENTS WITH D IAB E TE S TA B L E 3 Glycemic goals for older patients with diabetes.Fasting or pre-prandial glucose level (mmol L −HbA 1c indicates glycated hemoglobin; examples of hypoglycemia-inducing drugs include insulin, sulfonylureas, meglitinides, etc.; the HbA 1c , fasting, or pre-prandial blood glucose and bedtime glycemic goals are derived from the Treatment of Diabetes in Older Adults Guideline Resources issued by the American Endocrine Society.Key Consideration should be given to the benefit-to-risk ratio in setting glycemic goals for older patients with diabetes.(A) Stratified goals should be set for glycemic control according to the health status of older patients.(B) 3. HbA 1c and point glucose levels can be used as indicators for the assessment of glycemic control in older patients with diabetes.(A) 4. Glucose variability should be monitored; when necessary, indexes of glucose variability can be used as supplementary indicators for glycemic goals.(C) Strict control of blood glucose in older patients with diabetes provides limited benefits and somewhat increases the risk of hypoglycemia, which is extremely harmful to older patients and should be avoided to the greatest extent possible.Therefore, assessing treatment plans by considering the benefit-to-risk ratio is critical.Stratifying older patients and setting individualized glycemic goals are important.For older patients with diabetes with poor health status (Group 3), glycemic goals can be relaxed to some extent.However, the following consequences of less stringent blood glucose control must be avoided: (1) clear symptoms of diabetes; (2) elevated risk of infection; and (3) hyperglycemic crisis.

(B) 3 .
Assess the nutritional status of older patients with diabetes and identify malnutrition as early as possible; pay attention to appropriately increasing the protein and energy intake when developing the nutritional treatment regimen.(A) 4. Exercise risk and physical fitness should be assessed for older patients with diabetes before starting their exercise therapy.(A) 5. Encourage older patients to choose appropriate exercises that that can be sustained over the long term (e.g., aerobic exercise, resistance exercise, etc.), prevent older patients from falling during the exercise, be vigilant about hypoglycemia during and after exercise, and give timely treatment once it occurs.(B) It plays a crucial role in achieving the goals of blood glucose, blood pressure, and lipids; maintaining a healthy weight; and preventing or delaying complications associated with diabetes.First, the nutritional status of older patients with diabetes should be assessed.The Nutrition Risk Screening 2002 (NRS-2002), Short-Form MiniNutritional Assessment (MNA-SF), and other malnutrition screening tools should be adopted periodically to identify patient's nutrition risk.Malnutrition in older patients may cause a series of issues such as prolonged length of hospital stay, increased medical expenses, and increased re-hospitalization rate, etc.Therefore, early identification and management of malnutrition can help prevent and delay the occurrence and progression of complications.
73 SGLT2 inhibitors are Grade 1 glycemic drugs for older patients with T2DM and are recommended as the first choice for older patients with established/high risk of ASCVD, HF, and CKD.CVOTs have indicated that empagliflozin and canagliflozin decrease the risk of 3P-MACE in patients with T2DM and have demonstrated consistent results

73 m 2 )
−1  , canagliflozin and ertugliflozin are not recommended.If the eGFR is <30 mL min −1 (1.73 m 2 ) −1 , henagliflozin is not recommended, and canagliflozin and ertugliflozin are prohibited.If the eGFR is <25 mL min −1 (1.73 m 2 ) −1 , dapagliflozin should not be initiated, whereas for an eGFR <20 mL min −1 (1.73 m 2 ) −1 , GLP-1RAs are recommended as first-choice drugs for older patients with established/high risk of ASCVD.They can serve as an alternative treatment for older patients with CKD who cannot tolerate SGLT2 inhibitors.GLP-1RAs are generally Grade 2 glycemic drugs for older patients but are among the Grade 1 recommendations for patients with established/high risk of ASCVD.Dulaglutide significantly reduces 3P-MACE for T2DM patients with cardiovas-

3 )
. Compared with multi-injection insulin therapy, a fixed combination of basal insulin and GLP-1RAs, biphasic insulin, and basal insulin combined with oral glycemic drugs require fewer administration injections and thus enables a simplified regimen.Older patients with diabetes who can achieve glycemic goal with non-insulin therapy should gradually decrease their insulin dose until insulin is discontinued.Otherwise, patients relying on insulin for blood glucose control should receive the simplest possible insulin therapy, with the following considerations: (1) Minimize the frequency of injections; (2) Use long-acting or ultra-long-acting insulin analogues to regulate fasting and pre-prandial blood glucose to a satisfactory level.If postprandial glucose goals are not met, mealtime insulin may be considered.If patients have no contraindications, switching to a fixed combination of basal insulin and GLP-1RAs, biphasic insulin, or basal Fixeddose combination (FDC) and fixed-ratio combination (FRC) are combination of two or more drugs in a fixed dose or ratio, which are important forms of combined medication.FDC and FRC have many advantages, such as suitability for a variety of pathophysiological mechanisms, simplified regimens, and diminished medication burdens on patients. 118These regimens usually improve compliance and satisfaction among older patients.Because the clinical advantages and limitations of fixed combination therapies depend on the components, their clinical use should be based on considerations of the overall condition of older patients.Currently approved fixed combination therapies in China include metformin-based FDC, as well as FRC of basal insulin and GLP-1RAs.
tus of older patients.Those with good (Group 1) or intermediate (Group 2) overall health assessment results require individualized glycemic therapies according to the presence of established/high risk of ASCVD, HF, or CKD.The treatment pathways may include non-insulin therapies for (1) older patients with T2DM without established/high risk of ASCVD, HF, or CKD (Figure1), or (2) older patients with established/ high risk of ASCVD, HF, or CKD (Figure2), as well as (3) insulin therapies for older patients with T2DM (Figure3).The short-term insulin treatment pathway for older patients with T2DM is shown in Figure4.If the glycemic goal is not achieved have concurrent established/high risk of ASCVD, priority should be given to glucose-lowering medications with cardiovascular protective effects, including GLP-1RAs or SGLT-2 inhibitors with evidence-based medicine support.Age itself is a risk factor for ASCVD, and ASCVD is also an important cause of disability and death in older people without diabetes.Furthermore, smoking, obesity and overweight, hypertension, and dyslipidemia are all important risk factors that contribute to the occurrence of ASCVD in older patients with diabetes.Most older patients with diabetes have multiple co-existing cardiovascular risk factors and/or cardiovascular disease and kidney disease.However, older people are a heterogeneous group, and clinical research tends to exclude older patients with diabetes with advanced age and poor physical status; consequently, relevant data on older patients with diabetes are limited, and no consensus has been reached regarding the risk factors for ASCVD.

Key points 1 .
In older patients with diabetes mellitus with established/ high risk of ASCVD, glucose-lowering medications should preferentially include GLP-1RAs with cardiovascular protective effects or SGLT-2 inhibitors.(A) 2. The control goal of systolic blood pressure (SBP) in older patients with diabetes is below 130 mmHg; however, vigilance is necessary regarding the risk of hypotension.(B) 3. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are preferred for the treatment of hypertension and should not be co-administered; calcium channel blockers, diuretics, and β-blockers are drug candidates for potential coadministration with ACEIs or ARBs.(A) 4. Statin medications can decrease the risk of cardiovascular events in older patients with diabetes mellitus.

(
75-150 mg day −1 ) aspirin is recommended for secondary prevention.(A) 6. Older patients with diabetes are encouraged to actively cease smoking to decrease the risk of ASCVD.(A) 7. Body weight management in older patients with diabetes should consider both the body mass index and body composition.(B)

5 . 12 | 1 |
Body weight management: Obesity is associated with various cardiovascular diseases and can directly or indirectly increase cardiovascular disease incidence and mortality.Weight loss can improve blood glucose control and reduce other cardiovascular risk factors.However, weight loss interventions in older patients with diabetes mellitus should consider the their characteristics, such as body composition and risks of malnutrition, sarcopenia, and osteoporosis.As individuals age, they experience changes characterized by muscle loss and increased fat deposition.The body mass index (BMI) has limitations in reflecting obesity in older adults.When assessing obesity in older individuals, considering the BMI, the waist circumference, waist-to-hip ratio, and body muscle mass is recommended.A comprehensive evaluation of body weight, body composition, and muscle function should be conducted to develop weight management strategies.Dietary interventions for weight loss should avoid malnutrition and appropriately increase protein intake.Weight loss through diet alone without resistance exercise can lead to loss of lean tissue (muscle and bone), thus exacerbating ageassociated sarcopenia and loss of bone mass. 158Encouraging older patients with diabetes mellitus to engage in resistance training is important to increase body muscle mass.For older patients with both obesity and diabetes, choosing medications that can achieve both weight loss and glucose lowering is recommended.GLP-1 RAs (such as liraglutide, dulaglutide, and semaglutide) with evidence of strong weight loss intensity and cardiovascular protection should be preferred.If those medications are not tolerated, SGLT-2 inhibitors with moderate intensity of weight loss can be considered as an alternative.CHAP TER 10 : SCREENING AND TRE ATMENT OF CHRONI C COMPLI C ATI ON S OF D IAB E TE S IN OLDER PEOPLE 12.Diabetic kidney disease Diabetic kidney disease (DKD) is the major cause of CKD in China. 159Some people with T1DM develop DKD after a disease course of 5 to 10 years, whereas patients with T2DM might have nephropathy at the time of diagnosis.If not controlled, DKD can eventually develop into end-stage renal disease, thus severely affecting quality of life

1 .
and/or decreased eGFR, and by ruling out CKD caused by other Key points Older patients with diabetes should undergo renal function assessment at the time of diabetes are diagnosed and thereafter on a yearly basis.(A) 2. The degree of nephropathy should be screened and evaluated with a combination of two methods: urine albumin/creatinine ratio and eGFR.(A) 3. SGLT2 inhibitors are preferred for older patients with diabetes and CKD.In cases of intolerance or contraindications, GLP-1RAs with evidence of renal protection should be considered.(B) 4. ACEIs or ARBs treatment should be used for antihypertensive therapy.(B) 5.The non-steroidal mineralocorticoid receptor antagonist finerenone is recommended to delay the progression of kidney disease in older patients with diabetes and concomitant CKD and proteinuria.(A) 6. Chronic kidney disease in older patients with diabetes is usually caused by a variety of factors, and integrated management based on glucose-lowering therapy should be undertaken.(A) factors.Routine kidney aspiration biopsy is not recommended.Patients with DKD often have a long disease course and frequently have concurrent diabetic retinopathy (DR), manifesting primarily as proteinuria without gross hematuria, with a gradual decrease in eGFR.Notably, older people with diabetes who have diabetic renal damage usually have concurrent hypertension, hyperlipidemia, hyperuricemia, drug-induced renal damage, and other factors; The background colors in the table indicate the risk of CKD progression, with green representing low risk, yellow representing moderate risk, orange representing high risk, and red representing very high risk.The numbers in the table suggest the recommended frequency of annual reexamination.Abbreviations: eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; UACR, ratio of urinary albumin to creatinine.
accidents.Older patients with diabetes should undergo fundus examination at the time of diagnosis, should visit ophthalmologists for thorough checkups as needed, and should be screened at least once per year thereafter.Annual screenings should include visual acuity, intraocular pressure, ocular surface, and fundus examination, with a focus on diabetic retinopathy (DR) and macular edema.Additionally, assessment for cataracts, glaucoma, and dry eye syndrome should be performed.

12. 2 . 1 | 2 . 1 .
Diabetic fundus diseases 1. DR: DR, a common microvascular complication of diabetes, causes severe retinal damage and significantly affects quality of life.According to the disease stage, DR can be divided into non-proliferative DR and proliferative DR.The manifestations of non-proliferative DR include microaneurysm formation and intraretinal hemorrhage, wherein microvascular injury can increase vascular permeability (retinal edema and effusion); proliferative DR manifests as neovascularization in the optic disc, retina, iris, and chamber angle, thus eventually resulting in tractional retinal detachment and neovascular glaucoma.Routine DR screening is recommended for older patients with diabetes at the time of diagnosis.Subsequent annual follow-ups are advised for those with no DR or mild non-proliferative DR, or once every 6 months in cases of moderate non-proliferative DR, or once every 3 months in cases of severe non-proliferative DR and proliferative DR. 170 Long disease courses and suboptimal glycemic control are the risk factors for the occurrence and progression of DR; in addition, albuminuria, hypertension, and hyperlipidemia are risk factors for DR.Therefore, improvements in blood glucose, blood pressure, and blood lipids may aid in decreasing the occurrence of DR.Meta-analyses have indicated a significant association between GLP-1RAs, as compared with a placebo, and the risk of early DR.However, in comparison to insulin, GLP-1RAs have shown protective effects against advanced DR. 171 A meta-analysis of CVOT data on GLP-1RAs has not found a direct association between GLP-1RAs and DR, but has found a correlation with decreased HbA 1c . 172Monitoring retinal status, particularly for patients with proliferative DR and/or severe DR, is essential during strict blood glucose management with GLP-1RAs or other hypoglycemic agents.The relationship between GLP-1RAs and DR may be influenced by factors such as the type of agonist, patient sex, age, and disease duration. 171Data specific to the older diabetic population regarding the association between GLP-1RAs and DR are currently lacking.Pan-retinal laser photocoagulation is the major treatment method for proliferative DR, and intravitreous anti-vascular endothelial growth factor (VEGF) is another effective treatment.Diabetic macular edema (DME): DME is a disease of fluid accumulation in the central fovea of the macula, resulting from bloodretina barrier failure, and leading to extensive capillary leakage and subsequently diffuse edema.DME is common in older people with diabetes and may be accompanied by DR or may occur alone; this condition is a major contributor to visual impairment in people with diabetes.Optical coherence tomography is the gold standard for diagnosing DME and can be used for screening, classification, monitoring, and assessing treatment efficacy.Fluorescein angiography provides information on vascular leakage and barrier function.Older patients with diabetes are recommended to undergo screening for DME by optical coherence tomography at the time of diagnosis and thereafter once yearly, and if necessary, to undergo Key points Older patients with diabetes should be screened for diabetic fundus lesions at the time of diagnosis and once yearly thereafter; if fundus lesions are found, the frequency of reexamination should be increased.(A) 2. Beyond the fundus, attention should be paid to abnormalities in visual acuity, intraocular pressure, and the ocular surface in older patients with diabetes.(C) fluorescein angiography.For clinically significant macular edema (located in the central macula or threatening the central macula), follow-up examinations should be conducted every 3 months.In the past, focal/grid laser photocoagulation was the standard treatment for DME.In recent years, VEGF therapy has gained recognition, and the 2017 guidelines from the European Society of Retina Specialists recommend VEGF therapy as the first choice for treat-

1 . 2 . 3 .
but nationwide epidemiological survey data on older patients with diabetes with DSPN are currently lacking.In the Beijing region, data have indicated a prevalence of 42.6% for DSPN and of 26.2% for suspected DSPN among older individuals with T2DM. 185Clinically, DSPN manifests as numbness, pain, and paresthesia of the bilateral extremities.Newly diagnosed older patients with diabetes should undergo DSPN assessment, including a thorough medical history as well as assessment of small-fiber function (temperature sensation and pricking pain sensation) and large-fiber function (pressure sensation, ankle reflexes, and vibration sensation), with follow-up once yearly thereafter.Moreover, these patients should undergo 10 g nylon monofilament testing every year to promote the early identification of the risk of foot ulcers and limb amputation.Currently, no effective treatment is available to reverse DSPN.After a diagnosis of DSPN is considered, treatment should be initiated as early as possible to delay DSPN progression.Glycemic control is the main means of preventing DSPN and delaying its progression.Comprehensive management addressing various risk factors such as blood pressure and lipid levels also contributes to delaying DSPN progression.For patients with DSPN, integrated management goals should be formulated to address the aforementioned risk factors.In addition, data suggest that treatments such as methylcobalamin for nutritional support to nerves, alpha-lipoic acid for antioxidant stress, prostaglandin E1 for microcirculation improvement, and the aldose reductase inhibitor epalrestat have efficacy in treating older patients with DSPN.12.3.2| CAN Nationwide epidemiological data on CAN in older individuals with diabetes are currently lacking.Data from the Beijing region indicate a high prevalence of CAN, affecting 55.7% of older Key points Older patients with diabetes should be screened for distal symmetric polyneuropathy (DSPN) at the time of diagnosis and yearly thereafter.(A) Screening and treatment of diabetic autonomic neuropathy (DAN), particularly cardiac autonomic neuropathy (CAN), are important in older patients with diabetes.(B) Diabetic painful neuropathy severely affects quality of life in older patients with diabetes and consequently should be considered seriously.(B)

12. 3 . 3 |
Diabetic painful neuropathyDiabetic neuropathy may result in neuropathic pain through a variety of pathogenic mechanisms.Neuropathic pain typically manifests as burning pain, pricking pain, or shooting (electric shock) pain, accompanied by paresthesia, and may include multiple simultaneous symptoms that worsen in the nighttime.This pain disturbs daily life, jeopardizes quality of life, and may even cause disability and mental illness.Assessment and treatment of sleep and mood disorders are crucial.The most recent research from the American Neurological Association indicates that gabapentinoids, serotoninnorepinephrine reuptake inhibitors, sodium channel blockers, and tricyclic antidepressants (TCAs) can be used to treat pain caused by diabetic peripheral neuropathy.191Head-to-head trials have demonstrated therapeutic equivalence of gabapentinoids, serotoninnorepinephrine reuptake inhibitors, and TCAs in treating DPN

1 . 2 . 3 . 1 .
Diabetic foot refers to foot infection, ulcer, or even deep tissue damage caused by distal neuropathy and vasculopathy of the lower extremities in people with diabetes.This condition is one of the most serious chronic complications of diabetes, and severe cases can lead to amputation and death.Diabetic foot is associated with a variety of factors, predominantly peripheral arteriopathy and peripheral neuropathy; such factors also include trauma, infection, excessively high foot pressure due to foot deformity, and limited joint motion.Foot ulcers in Chinese patients with diabetes are primarily neuropathic and ischemic ulcers, or in rare cases are simple neuropathic ulcers or ulcers caused by Charcot foot deformity.196Because of poor vision, difficulty walking, and difficulty bending from the waist, older people with diabetes often have difficulty in self-examination or self-care of their feet, thus making early detection of foot problems difficult.Key pointsOlder patients with diabetes have an elevated incidence of lower extremity atherosclerotic disease, and patients with lower extremity atherosclerotic disease have an elevated risk of cerebro-cardiovascular events and diabetic foot.(B) For diabetic foot, prevention is better than treatment.The prognosis of diabetic foot can be improved by early identification of risk factors, intensive patient and family education, and interdisciplinary cooperative management.(B) Key points Hypoglycemia is an acute complication which older patients with diabetes should be especially vigilant of.To avoid hypoglycemia, reasonably individualized glycemic targets should be established, and glucoselowering medications with low risk of hypoglycemia should be selected.(A) 2. The hypoglycemia risk of elderly patients with T1DM may be reduced by wearing a continuous glucose monitoring system.(A) 3. The hyperglycemic crisis in older patients with diabetes often exists as a hyperglycemic hyperosmolar state, with the case fatality much higher than that of diabetic ketoacidosis.Fluid replacement is an important treatment approach, insulin should be used to lower blood glucose, and attention should be paid to potassium supplements.(B) 4. Lactic acidosis has a low morbidity but a high mortality and thereby should be taken seriously.(B) better than treatment.In the prevention of diabetic foot, attention should be paid to examining and eliminating risk factors for diabetic foot, educating patients and their families, and actively seeking interdisciplinary collaboration.The assessments and examinations include foot ulcer history taking and determining whether shoes are appropriate; whether protective sensation is lost; whether any vascular dysfunction is present (pulsation of dorsal pedal artery and posterior tibial artery); and whether foot deformity, callus, or pre-ulcerative lesion is present.Early identification and elimination of the above risk factors is the major measure to prevent diabetic foot ulcer.Education regarding diabetic foot can decrease the incidence198 and recurrence rates of diabetic foot ulcers.The education should include instructing patients to periodically examine their feet, particularly the interdigital spaces; periodically wash the feet and dry the interdigital spaces; avoid wearing tight socks or shoes; and check the shoes for any foreign bodies inside before donning.Older patients with diabetes should pay greater attention to foot care by199 : (1) checking the feet including the interdigital spaces every day, and if necessary, seeking help from the family or nursing personnel; (2) avoiding scalding and burning; (3) applying emollient oil or cream to dry skin, but not in the interdigital spaces; (4) directly clipping the nails crosswise, and trimming the edges and corners with a nail file; (5) avoiding use of any chemical agent or plaster to remove corns and calluses; (6) checking the shoes for any foreign bodies inside before donning; (7) avoiding walking barefoot; (8) undergoing periodic foot examinations by HCPs; (9) and seeking medical attention immediately if a foot skin blister, cut, scrape, or sore is found.The foot condition of older patients with diabetes must be actively assessed.For patients with diabetic foot, differentiating the etiology of ulcers (ischemic, neuropathic, or neuro-ischemic), the nature of gangrene (wet gangrene or dry gangrene), and performing diabetic foot classification (Wagner classification, Texas classification, etc.) are important.In China, the neuro-ischemic type of diabetic foot is more common, and treatment should focus on treating neuropathy, exercising, and reconstructing lower limb blood flow.Limb decompression, local debridement, and promotion of ulcer healing are essential.In cases of diabetic foot with infection, active anti-infective measures should be taken.After the occurrence of conditions such as a sharp change in skin color, aggravation of local pain with manifestations of inflammation such as redness and swelling, new ulcers, deterioration of an original superficial ulcer involving soft tissue and/or bone tissue, disseminated cellulitis, systemic infection signs, and osteomyelitis, prompt internal medicine treatment should be combined with assistance from vascular surgery, orthopedics, wound surgery, and other relevant specialties, and surgical treatment should be performed if necessary.Timely referral or multidisciplinary diagnosis and management can help improve the healing rate of foot ulcer and decrease the amputation rate. 20013 | CHAP TER 11: ACUTE COMPLI C ATI ON S OF D IAB E TE S IN THE ELDERLY Hypoglycemia, hyperglycemic hyperosmolar state (HHS), and diabetic ketoacidosis (DKA) are severe acute complications of diabetes, requiring rapid identification, timely diagnosis, and active treatment.Hypoglycemia is an adverse reaction in the course of glucose-lowering therapy that can result in short-term and long-term adverse clinical outcomes and increase the mortality.Compared to non-elderly patients, older patients with diabetes are more likely to develop hypoglycemia and are at higher risk of mortality associated with hypoglycemia, requiring much attention from clinicians.DKA and HHS are characterized by insulin deficiency and severe hyperglycemia.Clinically, these two conditions only differ in the degree of dehydration and severity of metabolic acidosis.The prognosis and outcome of DKA or HHS patients depends on the age, severity of dehydration, comorbidity, and whether the disease is treated in a timely and standardized manner.The prognosis and outcome of older patients with diabetes who have DKA and HHS are usually worse than those younger patients with diabetes.

3 .
Clinical manifestations: Typical hypoglycemic symptoms include sympathetic excitation symptoms such as sweating, palpitation, and shaky hands, as well as symptoms of impaired brain function.However, in older patients with diabetes, hypoglycemia shows a great heterogeneity in its clinical manifestations and is usually not manifested as sympathetic excitation symptoms,207 but as dizziness, blurred vision, conscious disturbance, and other impaired brain function symptoms.Nocturnal hypoglycemia can be manifested as reduced sleep quality and nightmare.Clinically, physicians should be highly vigilant about atypical hypoglycemic symptoms of older patients with diabetes.Older patients with diabetes are very likely to develop severe hypoglycemia due to decreased neurological responses and a lower threshold of response to hypoglycemia.Compared to non-elderly diabetic The clinical manifestations of HHS include hyperglycemic symptoms, dehydration symptoms, and neurologic symptoms.It is manifested as olydipsia, polydipsia, indifference, somnolence, and even hallucinations, epileptic seizure, and coma in patients.Due to poor skin elasticity of the elderly, the signs of dehydration are more difficult to identify.The diagnostic criteria for HHS include: plasma glucose level ≥33.3 mmol L −1 , effective plasma osmolality ≥320 mOsm L −1 , absence of significant metabolic acidosis, and absence of severe ketosis.In terms of treatment, fluid replacement is the crucial initial step that can help restore the blood volume and renal perfusion, improve peripheral circulation, and lower the blood glucose level.For older patients with diabetes, excessively slow and insufficient fluid replacement is more likely to cause hypotension and prerenal renal insufficiency, while excess and excessively fast fluid replacement tend to cause pulmonary edema and cardiac insufficiency.Therefore, the speed of fluid replacement should be adjusted individually according to the blood pressure, renal function, and cardiac function status.Continuous intravenous insulin injection, active potassium supplement, and close monitoring of blood potassium should be performed to avoid malignant arrhythmia caused by blood potassium decreased.

Key points 1 .
Drugs that increase risk of heart failure should be used with caution and contraindicated in older patients with diabetes who are at high risk of heart failure or complicated with heart failure.(B) 2. SGLT-2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and are preferred for older patients with diabetes and concurrent heart failure.(A)

1 . 1 .
care setting, screening can be done by means of scales (SARC-F scale or SARC-F + Calf Circumference Scale), assess muscle strength and physical function, and lifestyle interventions can be considered for the possibility of sarcopenia.In addition to the screening and assessment tools above, the diagnosis of sarcopenia can be further clarified at a medical facility or clinical research center by determining the amount of skeletal muscle in the extremities.Key points Bone mineral density (BMD) measurement by dualenergy X-ray absorptiometry and the fracture risk assessment tool FRAX suggests the fracture risk of older patients with diabetes but may underestimate such risk.(B) 2. Older patients with diabetes and comorbid osteoporosis should be cautious about using medications that may increase the risk of osteoporosis or fractures.(B) Key points Older patients with diabetes should be actively assessed for geriatric syndrome.(B) 2. The high prevalence of sarcopenia in older patients with diabetes is an important cause of frailty in these patients.(A) 3.All older patients with diabetes should be assessed for sarcopenia and frailty, so that early intervention can be given to improve their prognosis.(B) Alzheimer's disease.On the other hand, diabetics with cognitive dysfunction are prone to hypoglycemia.Cognitive dysfunction makes it difficult for older patients with diabetes to perform complex selfmanagement tasks,261 such as monitoring blood glucose and adjusting insulin dosage, and they also affect patients' eating times and meal rationalization.Early recognition of cognitive dysfunction is important in the management of diabetes in the elderly.Annual screening is recommended for older patients with diabetes for early detection of mild cognitive dysfunction or dementia.Simple and easy-to-use assessment tools are available to screen for cognitive impairment, such as the Mini-Mental State Examination (MMSE)262 and the Montreal Cognitive Assessment Scale (MoCA).263Modify the treatment regimen for diabetic patients with cognitive dysfunction by selecting medications with a low risk of hypoglycemia, while simplifying the treatment regimen and "de-intensifying therapy" if possible, with less stringent glycemic targets to avoid hypoglycemic and hyperglycemic crises.Metformin and GLP-1RAs may help improve cognitive function.

1 . 1 . 3 .
In view of the high prevalence of falls in older patients with diabetes, they should be assessed for fall risk to identify the risk factors for falls as early as possible and give early intervention.(C) 2. Fall prevention reduces fractures in older patients with diabetes.(C) Key points Hypoglycemia increases the dementia risk of patients, while diabetic patients with cognitive disorder are more likely to experience hypoglycemic events.(B) 2. Cognitive dysfunction is of particular importance in older patients with diabetes, and it is recommended to conduct annual screening to facilitate early identification of cognitive dysfunction and dementia in such patients.(B) For older patients with diabetes with cognitive dysfunction, less stringent glycemic targets should be implemented.(C) effects sulfonylureas, TZDs, DPP-4 inhibitors, and SGLT-2 inhibitors

14. 12 | 1 . 1 . 1 . 2 .
Skin problemsPatients with diabetes mellitus can develop a variety of skin lesions, including: (1) skin infections: bacterial, fungal, or viral infections;(2) skin diseases directly related to diabetes mellitus: diabetic maculopapular, acanthosis nigricans, etc.; (3) the skin manifestations of chronic complications of diabetes mellitus: skin ulcers or evenKey pointsOlder patients with diabetes have a variety of factors that can lead to sleep disturbances and should be concerned about their sleep.(B) 2. Intervention for sleep disorder can help improve the quality of sleep and life in older patients with diabetes, as well as improve blood glucose.(C) Key points Periodontitis is highly prevalent in older patients with diabetes, which increases the difficulty of glycemic control.(B) 2. Encourage older patients with diabetes to develop good hygiene habits and have regular oral examinations.(B) 3. Good glycemic control is conducive to the treatment of oral disorder, and in turn, the control of oral disorder is beneficial for the improvement of blood glucose.(B) Key points Focus on skin problems in older patients with diabetes and actively treat diabetes-induced skin lesions.(B).Poor glycemic control can exacerbate skin lesions, and skin lesions can lead to elevated blood glucose.(C).gangrene by diabetic foot; (4) the skin changes due to diabetes mellitus treatment: for example, subcutaneous fat proliferation, subcutaneous fat reduction, etc., caused by the injection of insulin.

16. 6 |
Palliative care Special management different from other periods should be carried out for older patients with diabetes who enter their end stage of life.In this stage, maintaining a patient's dignity, reducing pain, and guaranteeing quality of life are of vital importance.Patients have the right to reject examinations and treatment; HCPs should consider reducing diagnostic examinations and unnecessary treatment.Whenever possible, the HCPs, the patient, and his/her family should all participate in the medical decision-making process.In this stage, stringent management of blood glucose, blood pressure, and blood lipids are not the primary goal; palliative care with the aim of reduction in the frequency of blood glucose monitoring, prevention of hypoglycemia and hyperglycemic crisis, and alleviation of patient's pain and other discomforts should be carried out to improve patient's quality of life.With respect to the choice of glucose-lowering regimen, OGLMs can be used as first-line medications, but it is not suggested to use drugs associated with gastrointestinal adverse reactions; if necessary, basal insulin can be given.Patients with T2DM and organ damage should decrease the dosage of medications

17 | 1 . 2 . 3 . 4 .
CHAP TER 15: T1DM AND REL ATED PROB LEMS IN THE OLDER PATIENTS Older patients with T1DM refer to T1DM patients aged 65 years or older, including those diagnosed before, at, and after the age of Key points With the improvement in medical care, the number of older patients with T1DM will increase significantly.(C) Glycemic goals and treatment strategy should be individualized for older patients with T1DM.(C) For older T1DM patients with cognitive decline or decline in physical function, the treatment strategy should be as simple as possible, and meanwhile nursing support should be strengthened.(C) For older patients with T1DM, the use of CGM or insulin pumps can improve glycemic control and reduce the incidence of hypoglycemia (B).
65 years.With the improvement of living standards and medical care, the life span of T1DM patients is prolonged, and the number of older patients with T1DM will increase significantly.The prevalence of T1DM in the elderly is relatively low, yet latent autoimmune diabetes in adults (LADA) is not uncommon in this age group.Compared with younger-onset patients, elderlyonset LADA patients have better residual pancreatic β-cell function, more pronounced insulin resistance, and more pronounced characteristics of metabolic syndrome.The proportion of positive pancreatic autoantibodies in elderly-onset LADA patients is similar to that in younger-onset LADA patients, but there is a significant difference in the HLA-DQ genetic background between the two groups.317

18 . 1 |
mentioned clinical trials have included few participants aged 70 and older.Due to the complexity of disease management, the selfmanagement process of older patients with T1DM depends on their good cognitive ability.Older T1DM patients with severe hypoglycemia are more likely to have cognitive decline; therefore their insulin therapy regimen should be simplified.T1DM may cause decline in physical function of the elderly, which results in decreased self-management ability of older patients with T1DM; therefore, nursing support should be strengthened.Older patients with T1DM who are unable to live independently require assistance from nursing personnel in eating, activities, and injection of insulin.There is a relative lack of evidence-based medical proof for blood pressure, blood lipid, and proteinuria management in older patients with T1DM.Clinicians should determine the treatment goal and strategy based on the individual condition of each patient.18 | CHAP TER 16: D IAB E TE S MANAG EMENT-REL ATED TECHNOLOG IE S Blood glucose monitoring Blood glucose monitoring techniques include self-monitoring of blood glucose, CGM, glycated albumin, and HbA 1c , etc.
is required, and patients whose condition (especially those with T1DM) permit can wear continuous glucose monitoring.(B) 2. Time in range is a new supplementary target for evaluating patients' glycemic control level.(B) 3. The insulin injection method should be correctly mastered and attention should be paid to induration, adipose hyperplasia, and atrophy caused by the injection therapy.(B) 4. Insulin pump may improve glycemic control, but it is necessary to educate patients and their families on knowledge about insulin pumps, so that insulin pump-related complications can be avoided.(B)

18. 2 |
Injection techniquesCorrect subcutaneous insulin injection techniques include changing the needle after each injection, choosing an appropriate injection site, changing the injection site, taking care of the injection site appropriately, and avoiding intramuscular injection.The recommended injection sites include the abdomen, thigh, buttock, and upper arm.Long-term injection at the same site may cause local lipohypertrophy or lipoatrophy328 ; thus the injection site should be changed regularly and alternately.A survey conducted by the China IT IMPROVE study on Chinese diabetes patients, doctors, and nurses revealed that 34.7% of patients experienced fat hypertrophy at injection sites.The reuse of needles and improper rotation of injection sites increased the risk of fat hypertrophy by 3.15 times and 1.27 times, respectively, and also increased the risk of uncontrolled HbA 1c levels.329In older diabetes patients with conditions such as dementia, vision loss, neuropathy, poor mobility, and limited finger dexterity, there is an increased risk of missed or incorrectly administered insulin injections, and doctors are unable to accurately know the actual status of the patient's insulin injections.With continuous improvements in insulin injection pens, additional features have been developed and applied.Memory functions can record the dose and time of the last insulin injection, improving adherence to insulin therapy.330By connecting to smart devices such as smartphones with closerange wireless communication support, insulin injection records can be transmitted, visualized through applications, and shared.A prospective clinical study suggests that connected insulin pens can significantly reduce insulin injection omissions by 43%, improve TIR, and reduce TAR and TBR.331 Needle-free injection technology is one of the recommended injection methods in the "Chinese Diabetes Drug Injection Technology Guidelines."It can alleviate patients' needle phobia associated with traditional needle injection pens, reduce injection pain, thereby im- etc. Diabetes is classically divided into three types: upper, middle, and lower Xiaoke, and each has characteristic symptoms.The upper type is characterized by excessive thirst, the middle by excessive hunger, and the lower by excessive urination.TCM has a certain efficacy in the treatment of diabetes and its complications; however, because older patients often have declined organ function, multiple complications and comorbidities, and the combined use of Chinese and Western medicines is complex, patients should receive TCM treatment or combined traditional Chinese and Western medicine treatment under the guidance of a professional TCM practitioner and pay attention to medication safety during the treatment.ADL is activities of daily living.Number of impaired ADLs:________(Determined by assessment of the six aforementioned activities.If an

10 | CHAP TER 8: G LYCEMI C MED I C ATI ON S AND TRE ATMENT S TR ATEG IE S FOR OLDER PATIENTS WITH T YPE 2 D IAB E TE S
41ternating single-legged standing and walking in a straight line are effective ways to enhance balance.Tai chi, Baduanjin, Wuqinxi, and yoga can also improve coordination and balance.A meta-analysis found that tai chi has a positive effect on improving the ability of singlelegged standing in elderly patients with T2DM and improving blood glucose.41Balancetraining is recommended at least 2 to 3 times a week.
to CAN is highly important.Older patients with diabetes 190CAN is suspected, other concurrent diseases or concomitant drugs that may affect the cardiac autonomic nervous function should be further excluded.Patients with CAN and their families should be educated to prevent falls and avoid the occurrence of hypoglycemia, particularly nocturnal hypoglycemia.Research has indicated that combining aerobic exercise with resistance training improves heart rate variability in middle-aged and older female patients with T2DM, thus ameliorating CAN.189Medications such as midodrine, targeting the sympathetic nervous system, can be considered for treating orthostatic hypotension in older patients with diabetes.190 new-onset older patients with diabetes should be screened to exclude the possibility of pancreatic cancer.Some hypoglycemic agents may have a role in reducing tumor risk, including metformin 282 and DPP-4 inhibitors, 283 etc. one of the common types of sleep disorders, is typified by pathologic sleep fragmentation and is a respiratory sleep disorder that results in abnormal glucose metabolism, secondary hypertension, and multiple organ damage.OSAS leads to increased secretion of multiple stress hormones, aggravated glycemic variability, and increased difficulty in glycemic control.The prevalence of OSAS increases with age, Thus, the incidence of pruritus in older patients with di- 302ing hospitalization in a department of other disciplines other than endocrinology, clear glycemic goals are conducive to glycemic control.301According to the suggestions in Chinese Expert Consensus on the Blood Glucose Management of Inpatients,302older inpatients with diabetes whose CGA isGroup 1 specialists to manage the blood glucose of such patients.Conditions of inpatients may change within a short time, requiring timely identification and treatment regimen adjustment from physicians.In case of changes in patients' blood glucose levels due to application of glucocorticoid therapy, nasal feeding, total parenteral nutrition and dialysis, the glucose-lowering regimen should be reassessed in a timely manner.In addition, clinicians should always take a patient's age, life expectancy, overall health status, functional status, and cognitive ability into account, and weigh glycemic control and adverse reactions.
Travels independently or arranges own travel via taxi or travels on public transportation when assisted or accompanied by another Travel limited to taxi or automobile with assistance of another or does not travel at all Food preparation Plans, prepares, and serves adequate meals independently Prepares adequate meals if supplied with ingredients or needs to have meals prepared and served Note: IADL is instrumental activities of daily living.Number of impaired IADLs:________(Determined by assessment the aforementioned eight activities.If an individual is unable to perform an activity independently and requires assistance from others, it is to be considered as one impairment.The total number of impairments is calculated accordingly).